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This report is written by MaltSci based on the latest literature and research findings

How does neuroinflammation contribute to brain diseases? ​

Abstract ​

Neuroinflammation has emerged as a pivotal factor in the pathogenesis of various brain diseases, including neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as psychiatric conditions like depression and schizophrenia. This review synthesizes current research findings on the mechanisms and mediators of neuroinflammation, particularly the roles of glial cells, including microglia and astrocytes. The review highlights how microglial activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, contributing to neuronal damage and disease progression. In Alzheimer's disease, chronic neuroinflammation is linked to the accumulation of amyloid-beta plaques and tau tangles, exacerbating cognitive decline. Similarly, in Parkinson's disease, neuroinflammation correlates with dopaminergic neuron degeneration. The review also explores the implications of neuroinflammation in psychiatric disorders, emphasizing its contribution to mood regulation and symptom exacerbation. The therapeutic implications of targeting neuroinflammation are discussed, with a focus on emerging strategies that may modulate inflammatory responses to improve patient outcomes. Future research directions are outlined, emphasizing the need for a deeper understanding of the underlying mechanisms of neuroinflammation and the development of personalized medicine approaches to address these complex conditions.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 Neuroinflammation: Mechanisms and Mediators
    • 2.1 Role of Microglia in Neuroinflammation
    • 2.2 Astrocytes and Their Contribution to Inflammatory Responses
  • 3 Neuroinflammation in Neurodegenerative Diseases
    • 3.1 Alzheimer's Disease: The Inflammatory Hypothesis
    • 3.2 Parkinson's Disease and the Role of Inflammation
  • 4 Neuroinflammation in Psychiatric Disorders
    • 4.1 Depression: Linking Inflammation to Mood Disorders
    • 4.2 Schizophrenia and Neuroinflammatory Processes
  • 5 Therapeutic Implications and Future Directions
    • 5.1 Targeting Inflammation: Current and Emerging Therapies
    • 5.2 Future Research Directions in Neuroinflammation
  • 6 Conclusion

1 Introduction ​

Neuroinflammation has emerged as a pivotal factor in the pathogenesis of various brain diseases, encompassing neurodegenerative disorders, psychiatric conditions, and traumatic brain injuries. The brain's immune response, primarily mediated by glial cells such as microglia and astrocytes, plays a dual role in these processes, contributing both protective and detrimental outcomes. Chronic neuroinflammation is increasingly recognized as a hallmark of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), where persistent inflammatory signaling exacerbates neuronal loss and cognitive decline [1][2]. Moreover, neuroinflammation has been implicated in psychiatric disorders such as depression and schizophrenia, suggesting that inflammatory markers may serve as potential therapeutic targets [1].

The significance of understanding neuroinflammation lies in its complex interplay with neuronal health and disease. While acute neuroinflammation is essential for pathogen clearance and tissue repair, dysregulated and chronic inflammation can lead to neuronal damage and the progression of neurodegenerative diseases [3][4]. This understanding opens avenues for innovative therapeutic strategies aimed at mitigating the harmful effects of neuroinflammation while harnessing its protective potential. Research indicates that inflammatory processes, driven by the activation of microglia and astrocytes, are central to the initiation and progression of neuronal damage [1][1]. For instance, the role of chitinase-3-like protein 1 (CHI3L1) has been highlighted as a key inflammatory mediator involved in neurodegeneration [2].

Current research has made significant strides in elucidating the mechanisms underlying neuroinflammation and its contributions to neurodegenerative diseases. Studies have shown that neuroinflammation is associated with various neurological disorders, revealing the importance of immune cell activation and inflammatory mediator release in disease progression [1][5]. Key signaling pathways, including NF-κB and JAK-STAT, have been identified as crucial in mediating neuroinflammatory responses [6]. Furthermore, emerging evidence suggests that factors such as non-coding RNAs and epigenetic modifications play significant roles in the regulation of neuroinflammation [6].

The present review is organized into several sections to provide a comprehensive overview of the interplay between neuroinflammation and brain diseases. The first section delves into the mechanisms and mediators of neuroinflammation, focusing on the roles of microglia and astrocytes in inflammatory responses. The subsequent sections explore the implications of neuroinflammation in neurodegenerative diseases, specifically Alzheimer's disease and Parkinson's disease, highlighting the inflammatory hypotheses associated with these conditions. The review also addresses the impact of neuroinflammation on psychiatric disorders, including depression and schizophrenia, elucidating the links between inflammation and mood regulation. Finally, the therapeutic implications and future directions for research are discussed, emphasizing the potential for targeting neuroinflammation as a strategy for treating various brain diseases.

In summary, this review aims to synthesize current research findings on neuroinflammation and its contributions to brain diseases, identifying gaps in knowledge and outlining future research directions in this dynamic field. Understanding the dual role of neuroinflammation is crucial for developing effective therapeutic strategies that can mitigate its harmful effects while leveraging its protective potential, ultimately improving patient outcomes in neurodegenerative and psychiatric disorders.

2 Neuroinflammation: Mechanisms and Mediators ​

2.1 Role of Microglia in Neuroinflammation ​

Neuroinflammation is a complex and multifaceted response of the central nervous system (CNS) to various stimuli, including injury, infection, and neurodegenerative diseases. This process is primarily mediated by glial cells, particularly microglia, which are the resident immune cells of the brain. The activation of microglia plays a crucial role in the pathogenesis of numerous neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

Microglia are activated in response to pathological conditions, leading to the release of pro-inflammatory cytokines, chemokines, and other mediators that contribute to the inflammatory milieu in the CNS. For instance, upon encountering pathogens or damaged neurons, microglia undergo a transformation into a reactive state characterized by the secretion of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and reactive oxygen species (ROS). This activation is essential for the clearance of debris and pathogens, thus serving a protective role under acute conditions. However, when microglial activation becomes chronic, it can lead to detrimental effects, including neuronal damage and the progression of neurodegenerative diseases (Mushtaq et al. 2025; Niranjan 2018).

The dysregulation of microglial activation is particularly relevant in the context of neurodegeneration. Chronic neuroinflammation is implicated in the progression of diseases such as Alzheimer's, where the accumulation of amyloid-beta plaques and tau tangles triggers sustained microglial activation. This persistent inflammation can exacerbate neuronal death and synaptic dysfunction, ultimately contributing to cognitive decline (Adamu et al. 2024; Stacchiotti et al. 2025). Similarly, in Parkinson's disease, neuroinflammation has been shown to correlate with the degeneration of dopaminergic neurons in the substantia nigra, highlighting the importance of microglial activity in the disease's pathology (Wang et al. 2024).

Moreover, the mechanisms by which microglia contribute to neuroinflammation involve complex signaling pathways. For example, the NF-κB pathway is often activated in response to inflammatory stimuli, leading to the transcription of various pro-inflammatory genes. Additionally, microglial cells can interact with astrocytes and other immune cells, further amplifying the inflammatory response and creating a feedback loop that sustains neuroinflammation (Kim and Lee 2024).

The role of microglia is not solely detrimental; they also exhibit neuroprotective functions under certain conditions. For instance, they can adopt an anti-inflammatory phenotype that promotes tissue repair and neuronal survival. This duality underscores the need for a balanced microglial response, as both excessive activation and insufficient response can lead to pathological outcomes (Ding et al. 2021).

In summary, neuroinflammation, primarily mediated by microglial activation, is a critical factor in the pathogenesis of various brain diseases. While microglia play essential roles in maintaining homeostasis and responding to injury, their chronic activation and the resulting inflammatory milieu can lead to neuronal damage and exacerbate neurodegenerative processes. Understanding these mechanisms is vital for developing therapeutic strategies aimed at modulating neuroinflammation to mitigate the progression of neurodegenerative diseases (Fołta et al. 2025; Mushtaq et al. 2025; Niranjan 2018).

2.2 Astrocytes and Their Contribution to Inflammatory Responses ​

Neuroinflammation is a critical pathological feature that significantly contributes to the progression of various brain diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. It is characterized by the activation of glial cells, particularly microglia and astrocytes, which play pivotal roles in the inflammatory response within the central nervous system (CNS).

Astrocytes, the most abundant glial cells in the brain, are integral to maintaining homeostasis and supporting neuronal function. Under normal conditions, astrocytes perform essential functions, including metabolic support to neurons, regulation of blood flow, and maintenance of the blood-brain barrier. However, in response to injury or disease, astrocytes can undergo a process known as reactive astrogliosis, leading to their activation and altered function. This activation can result in the release of pro-inflammatory cytokines and chemokines, contributing to the neuroinflammatory milieu.

Research indicates that the activation of astrocytes during neuroinflammation can lead to a dichotomy in their role. While they can produce neuroprotective factors that support neuronal survival, they can also adopt a pro-inflammatory phenotype that exacerbates neuronal damage. For instance, activated astrocytes release inflammatory mediators such as interleukins (e.g., IL-1β, IL-6), tumor necrosis factor-alpha (TNF-α), and chemokines, which can promote the recruitment of immune cells to the site of injury and perpetuate the inflammatory response. This sustained inflammation can result in neuronal death, synaptic dysfunction, and ultimately contribute to the progression of neurodegenerative diseases [1].

Furthermore, the dysregulation of astrocytic functions during neuroinflammation has been linked to the exacerbation of neurodegenerative processes. For example, astrocytes can influence the activity of microglia, the resident immune cells of the CNS, which are also activated during neuroinflammatory responses. The interplay between activated astrocytes and microglia can create a feedback loop that amplifies neuroinflammation and leads to a detrimental cycle of neuronal injury [2].

In addition to their roles in inflammation, astrocytes are involved in the regulation of the extracellular environment, including the clearance of excess glutamate and the maintenance of ion homeostasis. However, during neuroinflammation, their ability to perform these functions may be compromised, leading to excitotoxicity and further neuronal damage [5]. This highlights the dual nature of astrocytes in neuroinflammation, where their protective roles can become detrimental under pathological conditions.

Overall, the contribution of neuroinflammation, particularly through the activation of astrocytes and their inflammatory responses, plays a crucial role in the pathogenesis of various brain diseases. Understanding these mechanisms is essential for developing targeted therapeutic strategies aimed at modulating neuroinflammation and mitigating its adverse effects on neuronal health and function [3][4].

3 Neuroinflammation in Neurodegenerative Diseases ​

3.1 Alzheimer's Disease: The Inflammatory Hypothesis ​

Neuroinflammation is increasingly recognized as a significant factor in the pathogenesis of neurodegenerative diseases, particularly Alzheimer's disease (AD). This condition is characterized by chronic inflammation within the central nervous system (CNS), which can lead to neuronal damage and cognitive decline. The inflammatory response in the brain is mediated by various immune cells, including microglia and astrocytes, which, when activated, release pro-inflammatory cytokines and other mediators that can exacerbate neuronal dysfunction.

In the context of Alzheimer's disease, neuroinflammation has been linked to several pathological features. Research indicates that the activation of glial cells in response to amyloid-beta (Aβ) plaques and neurofibrillary tangles contributes to a sustained inflammatory environment that accelerates neurodegeneration. For instance, the release of inflammatory mediators such as interleukins and tumor necrosis factor-alpha (TNF-α) is triggered by the activation of Toll-like receptors, which initiates an inflammatory cascade that is detrimental to neuronal health (Boleti et al., 2025; Ghosh et al., 2021).

Moreover, chronic neuroinflammation is associated with impaired synaptic plasticity, cognitive deficits, and progressive neurodegeneration. The persistence of inflammatory signals can lead to a cycle of damage, where neuronal loss further stimulates the inflammatory response, creating a feedback loop that exacerbates the condition (Fołta et al., 2025). This inflammatory milieu not only affects the survival of neurons but also impairs the ability of the CNS to regenerate, thus hindering recovery processes.

Recent studies have highlighted the dual role of neuroinflammation in Alzheimer's disease. While acute inflammation may serve a protective function, chronic inflammation is largely detrimental. This dichotomy is evident in the effects of inflammatory cytokines, which can promote both neuroprotection and neurotoxicity depending on the context and duration of their expression (Su & Su, 2025).

Furthermore, the dysregulation of the immune response in AD has been shown to involve both innate and adaptive immune mechanisms. Alterations in the activity of CD4+ T cells, for example, have been associated with increased neuroinflammatory responses, which may contribute to the pathogenesis of Alzheimer's disease (Princiotta Cariddi et al., 2022). This suggests that therapeutic strategies targeting neuroinflammation could hold promise for modifying disease progression.

In conclusion, neuroinflammation plays a crucial role in the development and progression of Alzheimer's disease. It contributes to neuronal dysfunction and death through the activation of glial cells and the release of pro-inflammatory mediators. Understanding the mechanisms underlying neuroinflammation may lead to novel therapeutic approaches aimed at modulating the inflammatory response, potentially improving outcomes for patients suffering from this devastating disease. Future research should focus on identifying specific pathways involved in neuroinflammation and exploring interventions that can effectively restore homeostasis within the CNS (Adamu et al., 2024; Niranjan, 2018).

3.2 Parkinson's Disease and the Role of Inflammation ​

Neuroinflammation plays a pivotal role in the pathogenesis of various neurodegenerative diseases, particularly Parkinson's disease (PD). The involvement of neuroinflammation in PD is characterized by the activation of glial cells, such as microglia and astrocytes, which release pro-inflammatory mediators that can exacerbate neuronal damage and contribute to disease progression.

In the context of PD, neuroinflammation is triggered by various factors, including the accumulation of misfolded proteins like α-synuclein, which can activate glial cells and initiate inflammatory responses. This activation leads to the production of neurotoxic factors, such as tumor necrosis factor alpha (TNF-α), interleukins, and reactive oxygen and nitrogen species, which collectively contribute to neuronal injury and death [7].

The interplay between neuroinflammation and neurodegeneration creates a self-sustaining loop where inflammation exacerbates neuronal damage, which in turn further activates inflammatory pathways. For instance, studies have shown that the chronic activation of microglia can lead to sustained neuroinflammation, resulting in a progressive loss of dopaminergic neurons in the substantia nigra, a hallmark of PD [8]. Furthermore, elevated levels of pro-inflammatory cytokines have been observed in the brains of PD patients, indicating a direct correlation between neuroinflammatory processes and the severity of the disease [9].

Research has highlighted the role of various inflammatory mediators and pathways in PD. For example, the nuclear factor kappa B (NF-κB) pathway is commonly activated in response to neurotoxic insults and is implicated in the regulation of pro-inflammatory cytokine expression [10]. Additionally, the involvement of immune cells, including T cells and monocytes, has been recognized as significant in the neuroinflammatory response associated with PD [5].

Recent findings suggest that neuroinflammation may also influence the gut-brain axis, where peripheral inflammation can affect central nervous system processes and contribute to neurodegenerative pathology [11]. The interaction between systemic inflammation and neuroinflammation underscores the complexity of the disease mechanisms at play.

In conclusion, neuroinflammation is a critical factor in the development and progression of Parkinson's disease. It operates through a multifaceted network of cellular and molecular interactions that promote neurodegeneration. Understanding these mechanisms is essential for identifying potential therapeutic targets aimed at mitigating neuroinflammatory responses and slowing disease progression [12].

4 Neuroinflammation in Psychiatric Disorders ​

4.1 Depression: Linking Inflammation to Mood Disorders ​

Neuroinflammation plays a significant role in the pathophysiology of various brain diseases, particularly psychiatric disorders such as depression. The relationship between neuroinflammation and depression is complex and bidirectional; neuroinflammation can contribute to the onset and exacerbation of depressive symptoms, while depression itself can provoke inflammatory responses.

Neuroinflammation is characterized by the activation of glial cells, particularly microglia, which are the resident immune cells in the central nervous system (CNS). When activated, microglia can adopt a pro-inflammatory (M1) phenotype, leading to the release of pro-inflammatory cytokines that disrupt neuronal function and contribute to mood disorders [13]. This inflammatory response can affect neurotransmitter systems, notably serotonin, which is crucial for mood regulation. Chronic inflammation can lead to increased levels of inflammatory mediators that impair serotonin synthesis and activate the hypothalamus-pituitary-adrenal (HPA) axis, further contributing to depressive symptoms [14].

Research indicates that the neuroinflammatory process involves various mechanisms, including the release of pro-inflammatory cytokines, activation of the HPA axis, and disruptions in neurotransmitter systems [15]. For instance, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been identified as a critical component in the neuroinflammatory response linked to depression. This inflammasome mediates pyroptosis, a form of inflammatory cell death that is implicated in neuroinflammatory-related diseases [16].

Furthermore, the bidirectional nature of the relationship means that individuals with depression often exhibit elevated levels of inflammatory markers, which can predict treatment responses to antidepressants [17]. This suggests that a subset of patients may have an inflammatory subtype of depression, characterized by unique symptom presentations and treatment responses that could be targeted with anti-inflammatory therapies [17].

The interplay between neuroinflammation and depression also highlights the role of environmental factors, such as stress, which can exacerbate neuroinflammatory responses and contribute to the development of depressive symptoms [18]. Chronic exposure to stressors can lead to sustained activation of microglia and increased production of inflammatory cytokines, creating a vicious cycle that complicates treatment and recovery [14].

In summary, neuroinflammation is a critical factor in the pathophysiology of depression and other psychiatric disorders. The activation of glial cells, the release of pro-inflammatory cytokines, and the resultant disruption of neurotransmitter systems all contribute to the onset and persistence of depressive symptoms. Understanding these mechanisms not only enhances our comprehension of depression but also opens avenues for novel therapeutic strategies targeting neuroinflammation to improve treatment outcomes for affected individuals [14][15][17].

4.2 Schizophrenia and Neuroinflammatory Processes ​

Neuroinflammation plays a significant role in the pathogenesis of schizophrenia and other psychiatric disorders, acting as a key contributor to the underlying mechanisms that drive these conditions. The intricate relationship between neuroinflammation and schizophrenia is supported by a wealth of evidence highlighting various pathways and biological interactions.

Schizophrenia is characterized by a complex interplay of cognitive, behavioral, and emotional dysregulations, which are often exacerbated by neuroinflammatory processes. Studies indicate that neuroinflammation in the central nervous system (CNS) may be linked to immune dysfunction, contributing to the disorder's pathophysiology. Specifically, the dysregulation of the WNT/β-catenin signaling pathway has been identified as a critical mechanism through which neuroinflammation influences schizophrenia. This pathway interacts with various inflammatory factors such as IL-6, IL-8, and TNF-α, alongside factors related to oxidative stress and neurotransmitter dysregulation, particularly involving dopamine and glutamate (Vallée 2022) [19].

The evidence for neuroinflammation in schizophrenia includes elevated levels of proinflammatory cytokines, aberrant microglial activation, and disruptions in the blood-brain barrier. These pathological features contribute to neuronal dysfunction and are associated with cognitive deficits and the manifestation of both positive and negative symptoms of the disorder (Huang et al. 2025) [20]. Moreover, systemic inflammation and microglial activation have been observed in patients with schizophrenia, indicating a potential link between peripheral inflammatory processes and central neuroinflammatory responses (Corsi-Zuelli et al. 2017) [21].

The relationship between inflammation and schizophrenia is further complicated by the observation that neuroinflammation may also influence metabolic processes. In particular, increased levels of proinflammatory cytokines are associated with changes in neurotransmitter systems that can exacerbate symptoms. For instance, alterations in brain monoamine levels due to inflammation may impair mood and cognitive functions, thus contributing to the clinical progression of schizophrenia (Bauer & Teixeira 2019) [18].

Therapeutically, addressing neuroinflammation presents a promising avenue for improving outcomes in schizophrenia. Anti-inflammatory strategies, including the use of non-steroidal anti-inflammatory drugs (NSAIDs), cytokine inhibitors, and antioxidants, have shown potential in modulating the inflammatory response and may help alleviate symptoms associated with the disorder (Huang et al. 2025) [20]. Additionally, the exploration of immunomodulatory drugs, such as clozapine, suggests that these agents may exert beneficial effects by targeting neuroinflammatory pathways (Amerio et al. 2024) [22].

In summary, neuroinflammation significantly contributes to the pathophysiology of schizophrenia through a complex interplay of inflammatory processes, neurotransmitter dysregulation, and immune system interactions. Understanding these mechanisms not only enhances the comprehension of schizophrenia's etiology but also opens new avenues for targeted therapeutic interventions aimed at mitigating neuroinflammatory responses.

5 Therapeutic Implications and Future Directions ​

5.1 Targeting Inflammation: Current and Emerging Therapies ​

Neuroinflammation is increasingly recognized as a pivotal factor in the pathogenesis of various neurological disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This complex immune response is characterized by the activation of glial cells, particularly microglia and astrocytes, which release pro-inflammatory cytokines, chemokines, and reactive oxygen species. While acute neuroinflammation serves a protective role by facilitating pathogen clearance and tissue repair, chronic and dysregulated inflammation can lead to neuronal damage, synaptic dysfunction, and ultimately neurodegeneration [6][23].

The mechanisms underlying neuroinflammation involve various signaling pathways, including NF-κB, JAK-STAT, and the NLRP3 inflammasome, which are crucial for the activation of glial cells and the subsequent inflammatory response [6]. Furthermore, the involvement of peripheral immune cells, such as monocytes, highlights the systemic nature of neuroinflammatory processes [5].

Therapeutically, the modulation of neuroinflammation presents a promising avenue for intervention in neurodegenerative diseases. Current strategies focus on several approaches, including pharmacological agents, bioactive molecules, and stem cell-based therapies aimed at restoring immune homeostasis and promoting neuroprotection [24]. Anti-inflammatory cytokines, such as IL-10 and TGF-β, have shown potential in mitigating neuroinflammation and its deleterious effects [25].

Emerging therapies also include the use of nanotechnology to enhance the delivery of anti-inflammatory agents across the blood-brain barrier (BBB), which remains a significant challenge in treating neuroinflammation [26]. These nanoparticle-based systems offer advantages such as improved biocompatibility and targeted delivery, thereby increasing the efficacy of treatments for neurodegenerative disorders [26].

Future directions in neuroinflammation research emphasize the need for personalized medicine approaches utilizing patient-specific models, such as human pluripotent stem cell-derived glia, to better understand the inflammatory mechanisms at play in individual patients [27]. Additionally, the integration of multidisciplinary strategies that address both the inflammatory and metabolic aspects of neurodegeneration is essential for developing effective therapeutic interventions [6].

In summary, neuroinflammation plays a crucial role in the progression of brain diseases, and targeting this inflammatory response through innovative therapeutic strategies holds significant promise for improving outcomes in patients with neurodegenerative disorders. Continued research into the underlying mechanisms and the development of targeted therapies will be vital in addressing the challenges posed by these complex conditions.

5.2 Future Research Directions in Neuroinflammation ​

Neuroinflammation plays a pivotal role in the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. It is characterized by a complex immune response within the central nervous system (CNS), involving the activation of glial cells, such as microglia and astrocytes, as well as the release of inflammatory mediators. This response can be beneficial in acute scenarios, aiding in pathogen clearance and tissue repair; however, when it becomes chronic or dysregulated, it contributes significantly to neuronal damage and disease progression.

Chronic neuroinflammation is driven by several factors, including the activation of microglia, which release pro-inflammatory cytokines and reactive oxygen species that can exacerbate neuronal injury and lead to synaptic dysfunction. This process is not merely a passive consequence of neurodegeneration; rather, it is a proactive phenomenon that fuels neuropathological changes. For instance, the loss of blood-brain barrier integrity during neurodegenerative processes allows for systemic inflammatory mediators to infiltrate the CNS, further intensifying the inflammatory response and contributing to neurodegeneration (Cervellati et al. 2020) [28].

Research has indicated that neuroinflammation is implicated in the initiation and progression of neurodegenerative diseases through various mechanisms. For example, microglia activation is linked to the release of neurotoxic factors that lead to neuronal cell death. Additionally, systemic factors such as metabolic dysregulation, infections, and microbiota alterations have been associated with neuroinflammatory processes (Niranjan 2018) [5]. Understanding these pathways is crucial for identifying potential therapeutic targets aimed at modulating neuroinflammation.

In terms of therapeutic implications, there is a growing interest in developing strategies that target neuroinflammation to slow down or reverse neurodegenerative processes. Current approaches include the use of anti-inflammatory drugs, immunomodulators, and bioactive compounds such as flavonoids, which have shown promise in reducing neuroinflammation and protecting neuronal health (Chen et al. 2022) [29]. Moreover, emerging therapies, including stem cell interventions and gene therapy, aim to restore immune homeostasis and promote regeneration in the affected brain regions (Karam et al. 2025) [24].

Future research directions should focus on elucidating the precise molecular mechanisms that underlie neuroinflammation and its interactions with neurodegenerative processes. Investigating the role of non-coding RNAs, epigenetic modifications, and the gut-brain axis in neuroinflammatory responses could provide deeper insights into their contribution to disease progression (Kim & Lee 2024) [6]. Additionally, advancing our understanding of the crosstalk between peripheral and central inflammation is essential, as it may reveal novel therapeutic avenues for managing neurodegenerative disorders (Geloso et al. 2024) [30].

Furthermore, the development of innovative delivery systems, such as nanoparticles, could enhance the targeting of anti-inflammatory agents to the brain, overcoming the challenges posed by the blood-brain barrier (Mahanta et al. 2025) [26]. Continued interdisciplinary collaboration and the integration of advanced technologies will be vital in translating these findings into effective clinical therapies that can mitigate the impact of neuroinflammation on neurodegenerative diseases.

6 Conclusion ​

This review highlights the critical role of neuroinflammation in the pathogenesis of various brain diseases, including neurodegenerative disorders and psychiatric conditions. The activation of glial cells, particularly microglia and astrocytes, is central to the inflammatory response, which can lead to both protective and detrimental outcomes. Key findings indicate that chronic neuroinflammation is a hallmark of conditions such as Alzheimer's disease and Parkinson's disease, where it exacerbates neuronal damage and cognitive decline. The review underscores the need for further research to elucidate the complex mechanisms underlying neuroinflammation and its interactions with neurodegenerative processes. Future studies should focus on developing targeted therapeutic strategies that can modulate neuroinflammation, restore homeostasis within the central nervous system, and ultimately improve patient outcomes. Emerging therapies, including anti-inflammatory drugs and novel delivery systems, hold promise for mitigating the effects of neuroinflammation. Overall, advancing our understanding of neuroinflammation is essential for addressing the challenges posed by neurodegenerative diseases and enhancing therapeutic interventions.

References ​

  • [1] Justyna Fołta;Zuzanna Rzepka;Dorota Wrześniok. The Role of Inflammation in Neurodegenerative Diseases: Parkinson's Disease, Alzheimer's Disease, and Multiple Sclerosis.. International journal of molecular sciences(IF=4.9). 2025. PMID:40507988. DOI: 10.3390/ijms26115177.
  • [2] Umar Mushtaq;Bilal Ahmad;Firdous A Khanday;Muzamil Ahmad. CHI3L1: An Emerging Player in Neuroinflammation and Neurodegeneration.. Molecular neurobiology(IF=4.3). 2025. PMID:41214238. DOI: 10.1007/s12035-025-05354-x.
  • [3] Torbjörn Bäckström;Magnus Doverskog;Thomas P Blackburn;Bruce F Scharschmidt;Vicente Felipo. Allopregnanolone and its antagonist modulate neuroinflammation and neurological impairment.. Neuroscience and biobehavioral reviews(IF=7.9). 2024. PMID:38608826. DOI: 10.1016/j.neubiorev.2024.105668.
  • [4] Alhamdu Adamu;Shuo Li;Fankai Gao;Guofang Xue. The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets.. Frontiers in aging neuroscience(IF=4.5). 2024. PMID:38681666. DOI: 10.3389/fnagi.2024.1347987.
  • [5] Rituraj Niranjan. Recent advances in the mechanisms of neuroinflammation and their roles in neurodegeneration.. Neurochemistry international(IF=4.0). 2018. PMID:30016687. DOI: 10.1016/j.neuint.2018.07.003.
  • [6] Mi Eun Kim;Jun Sik Lee. Mechanisms and Emerging Regulators of Neuroinflammation: Exploring New Therapeutic Strategies for Neurological Disorders.. Current issues in molecular biology(IF=3.0). 2024. PMID:39852123. DOI: 10.3390/cimb47010008.
  • [7] Rituraj Niranjan. The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson's disease: focus on astrocytes.. Molecular neurobiology(IF=4.3). 2014. PMID:23783559. DOI: 10.1007/s12035-013-8483-x.
  • [8] Karamjeet Kaur;Jaskamal Singh Gill;Puneet Kumar Bansal;Rahul Deshmukh. Neuroinflammation - A major cause for striatal dopaminergic degeneration in Parkinson's disease.. Journal of the neurological sciences(IF=3.2). 2017. PMID:28991704. DOI: 10.1016/j.jns.2017.08.3251.
  • [9] Carmela Spagnuolo;Stefania Moccia;Gian Luigi Russo. Anti-inflammatory effects of flavonoids in neurodegenerative disorders.. European journal of medicinal chemistry(IF=5.9). 2018. PMID:28923363. DOI: 10.1016/j.ejmech.2017.09.001.
  • [10] Mobina Fathi;Kimia Vakili;Shirin Yaghoobpoor;Mohammad Sadegh Qadirifard;Mohammadreza Kosari;Navid Naghsh;Afsaneh Asgari Taei;Andis Klegeris;Mina Dehghani;Ashkan Bahrami;Hamed Taheri;Ashraf Mohamadkhani;Ramtin Hajibeygi;Mostafa Rezaei Tavirani;Fatemeh Sayehmiri. Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.. Frontiers in aging neuroscience(IF=4.5). 2022. PMID:35912090. DOI: 10.3389/fnagi.2022.855776.
  • [11] G Arena;K Sharma;G Agyeah;R Krüger;A Grünewald;J C Fitzgerald. Neurodegeneration and Neuroinflammation in Parkinson's Disease: a Self-Sustained Loop.. Current neurology and neuroscience reports(IF=5.2). 2022. PMID:35674870. DOI: 10.1007/s11910-022-01207-5.
  • [12] Berçem Yeman-Kıyak;Tahire Yurdakul;Aslınur Selim;Birsen Elibol;Timuçin Avşar;Yeşim Neğiş;Mustafa Gani Sürmen;Rama Şeyhali-Abutayeh;Rümeysa Akbayır;Melike Cansel Eren;Pınar Öz;Burcu Çevreli;Sevim Işık. Early α-Synuclein Pathology Induces Neuroinflammation and Decreases Topoisomerase IIβ Expression in A53T Mice.. Inflammation(IF=5.0). 2025. PMID:41071263. DOI: 10.1007/s10753-025-02354-w.
  • [13] Xiaoyun Guo;Yanxia Rao;Ruizhi Mao;Lvchun Cui;Yiru Fang. Common cellular and molecular mechanisms and interactions between microglial activation and aberrant neuroplasticity in depression.. Neuropharmacology(IF=4.6). 2020. PMID:32980387. DOI: 10.1016/j.neuropharm.2020.108336.
  • [14] Andreea Sălcudean;Ramona-Amina Popovici;Dana Emanuela Pitic;Diana Sârbu;Adela Boroghina;Mohammad Jomaa;Matin Asad Salehi;Alsayed Ahmad Mhd Kher;Maria Melania Lica;Cristina Raluca Bodo;Virgil Radu Enatescu. Unraveling the Complex Interplay Between Neuroinflammation and Depression: A Comprehensive Review.. International journal of molecular sciences(IF=4.9). 2025. PMID:40004109. DOI: 10.3390/ijms26041645.
  • [15] Andreea Sălcudean;Cristina-Raluca Bodo;Ramona-Amina Popovici;Maria-Melania Cozma;Mariana Păcurar;Ramona-Elena Crăciun;Andrada-Ioana Crisan;Virgil-Radu Enatescu;Ileana Marinescu;Dora-Mihaela Cimpian;Andreea-Georgiana Nan;Andreea-Bianca Sasu;Ramona-Camelia Anculia;Elena-Gabriela Strete. Neuroinflammation-A Crucial Factor in the Pathophysiology of Depression-A Comprehensive Review.. Biomolecules(IF=4.8). 2025. PMID:40305200. DOI: 10.3390/biom15040502.
  • [16] Teng Wan;Xiaoyu Li;Mingyuan Fu;Xiaoyu Gao;Peiling Li;Weiming Guo. NLRP3-Dependent Pyroptosis: A Candidate Therapeutic Target for Depression.. Frontiers in cellular neuroscience(IF=4.0). 2022. PMID:35722622. DOI: 10.3389/fncel.2022.863426.
  • [17] Andrew H Miller. Advancing an Inflammatory Subtype of Major Depression.. The American journal of psychiatry(IF=14.7). 2025. PMID:40329642. DOI: 10.1176/appi.ajp.20250289.
  • [18] Moisés E Bauer;Antonio L Teixeira. Inflammation in psychiatric disorders: what comes first?. Annals of the New York Academy of Sciences(IF=4.8). 2019. PMID:29752710. DOI: 10.1111/nyas.13712.
  • [19] Alexandre Vallée. Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway.. International journal of molecular sciences(IF=4.9). 2022. PMID:35269952. DOI: 10.3390/ijms23052810.
  • [20] Hao Huang;Zijie Luo;Jieshu Min;Wenjie Luo;Xujia Zhou;Changxu Wang. Targeting Neuroinflammation in Schizophrenia: A comprehensive review of mechanisms and pharmacological interventions.. International immunopharmacology(IF=4.7). 2025. PMID:40424655. DOI: 10.1016/j.intimp.2025.114910.
  • [21] Fabiana Maria das Graças Corsi-Zuelli;Fernanda Brognara;Gustavo Fernando da Silva Quirino;Carlos Hiroji Hiroki;Rafael Sobrano Fais;Cristina Marta Del-Ben;Luis Ulloa;Helio Cesar Salgado;Alexandre Kanashiro;Camila Marcelino Loureiro. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor.. Frontiers in immunology(IF=5.9). 2017. PMID:28620379. DOI: 10.3389/fimmu.2017.00618.
  • [22] Andrea Amerio;Luca Magnani;Gabriele Arduino;Fabio Fesce;Renato de Filippis;Alberto Parise;Alessandra Costanza;Khoa D Nguyen;Daniele Saverino;Domenico De Berardis;Andrea Aguglia;Andrea Escelsior;Gianluca Serafini;Pasquale De Fazio;Mario Amore. Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia.. Current neuropharmacology(IF=5.3). 2024. PMID:38031778. DOI: 10.2174/1570159X22666231128101725.
  • [23] Fatima Cheataini;Nissrine Ballout;Tareq Al Sagheer. The effect of neuroinflammation on the cerebral metabolism at baseline and after neural stimulation in neurodegenerative diseases.. Journal of neuroscience research(IF=3.4). 2023. PMID:37186320. DOI: 10.1002/jnr.25198.
  • [24] Marie Karam;Alba Ortega-Gascó;Daniel Tornero. Emerging Insights into Brain Inflammation: Stem-Cell-Based Approaches for Regenerative Medicine.. International journal of molecular sciences(IF=4.9). 2025. PMID:40244116. DOI: 10.3390/ijms26073275.
  • [25] Costanza Stacchiotti;Simona Mazzella di Regnella;Miriam Cinotti;Alida Spalloni;Elisabetta Volpe. Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.. International journal of molecular sciences(IF=4.9). 2025. PMID:40332510. DOI: 10.3390/ijms26083854.
  • [26] Arun Kumar Mahanta;Avinash Gothwal;Bivek Chaulagain;Chinenye Edith Muolokwu;Benjamin Tagoe;Babita Lamsal;Matheus Belin;Jagdish Singh. Emerging anti-inflammatory nanosystems targeted to the brain.. Nanomedicine (London, England)(IF=3.9). 2025. PMID:40856754. DOI: 10.1080/17435889.2025.2552103.
  • [27] Srishti Kala;Andrew G Strutz;Moriah E Katt. The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation.. Neurology international(IF=3.0). 2025. PMID:39852770. DOI: 10.3390/neurolint17010006.
  • [28] Carlo Cervellati;Alessandro Trentini;Alessandra Pecorelli;Giuseppe Valacchi. Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery.. Antioxidants & redox signaling(IF=6.1). 2020. PMID:32143546. DOI: 10.1089/ars.2020.8076.
  • [29] Yu Chen;Fu Peng;Ziwei Xing;Junren Chen;Cheng Peng;Dan Li. Beneficial effects of natural flavonoids on neuroinflammation.. Frontiers in immunology(IF=5.9). 2022. PMID:36353622. DOI: 10.3389/fimmu.2022.1006434.
  • [30] Maria Concetta Geloso;Luca Zupo;Valentina Corvino. Crosstalk between peripheral inflammation and brain: Focus on the responses of microglia and astrocytes to peripheral challenge.. Neurochemistry international(IF=4.0). 2024. PMID:39362496. DOI: 10.1016/j.neuint.2024.105872.

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