Neuroinflammation in Neurodegeneration

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Neuroinflammation in Neurodegeneration

Introduction

Neuroinflammation represents a fundamental pathological mechanism that underlies virtually all neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), frontotemporal dementia (FTD), and multiple sclerosis (MS). This comprehensive page explores the molecular and cellular processes involved in neuroinflammation, their contribution to disease progression, and emerging therapeutic strategies aimed at modulating this deleterious inflammatory response. [@neuroinflammation_definition]

Unlike acute inflammation, which serves protective functions, chronic neuroinflammation becomes self-perpetuating and drives progressive neuronal loss. The inflammatory cascade involves the coordinated activation of resident glial cells—primarily microglia and astrocytes—along with peripheral immune cells that infiltrate the brain parenchyma. This activation leads to the release of pro-inflammatory cytokines, chemokines, reactive oxygen species (ROS), reactive nitrogen species (RNS), and lipid mediators that collectively orchestrate a destructive biochemical environment. [@microglial_activation]

Cellular Components of Neuroinflammation

Microglia: The Resident Immune Sentinels

...

Neuroinflammation in Neurodegeneration

Introduction

Neuroinflammation represents a fundamental pathological mechanism that underlies virtually all neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), frontotemporal dementia (FTD), and multiple sclerosis (MS). This comprehensive page explores the molecular and cellular processes involved in neuroinflammation, their contribution to disease progression, and emerging therapeutic strategies aimed at modulating this deleterious inflammatory response. [@neuroinflammation_definition]

Unlike acute inflammation, which serves protective functions, chronic neuroinflammation becomes self-perpetuating and drives progressive neuronal loss. The inflammatory cascade involves the coordinated activation of resident glial cells—primarily microglia and astrocytes—along with peripheral immune cells that infiltrate the brain parenchyma. This activation leads to the release of pro-inflammatory cytokines, chemokines, reactive oxygen species (ROS), reactive nitrogen species (RNS), and lipid mediators that collectively orchestrate a destructive biochemical environment. [@microglial_activation]

Cellular Components of Neuroinflammation

Microglia: The Resident Immune Sentinels

Microglia are the resident innate immune cells of the central nervous system (CNS), originating from yolk sac progenitors during embryonic development. In the healthy brain, microglia exist in a surveillance state characterized by small cell bodies and highly ramified processes that continuously scan the surrounding environment. These cells express pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and triggering receptor expressed on myeloid cells 2 (TREM2) that enable detection of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). [@trem2]

Upon encountering pathological stimuli, microglia undergo dramatic morphological and functional transformations, adopting distinct activation states:

Mermaid diagram (expand to render)

The M1 phenotype represents the classically activated, pro-inflammatory state characterized by the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), interleukin-18 (IL-18), nitric oxide (NO), and ROS. These cells upregulate major histocompatibility complex (MHC) class II molecules and costimulatory signals, enabling antigen presentation. Prolonged M1 activation leads to microglial priming, a hyperresponsive state where subsequent inflammatory challenges trigger exaggerated responses.

The M2 phenotype represents the alternatively activated, anti-inflammatory state that promotes tissue repair and homeostasis. M2 microglia secrete neurotrophic factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and transforming growth factor-beta (TGF-beta). They express markers including CD206 (mannose receptor) and Arginase-1 (Arg1), and participate in debris clearance and wound healing.

Disease-Associated Microglia (DAM) represent a recently identified population that emerges in neurodegenerative conditions. DAM exhibit a distinct transcriptional signature characterized by upregulation of disease-specific genes including TREM2-dependent genes, APOE, and CST3. These cells appear to represent an attempt at compensation—attempting to clear pathological protein aggregates—but may become dysfunctional over time. [@trem2]

Astrocytes: The Multifunctional Glial Partners

Astrocytes constitute the most abundant glial cell type in the human brain and play essential roles in maintaining CNS homeostasis. In response to neuroinflammation, astrocytes undergo a process termed reactive astrogliosis, characterized by upregulation of glial fibrillary acidic protein (GFAP), cellular hypertrophy, and proliferation. Reactive astrocytes adopt phenotypically distinct states that profoundly influence disease outcomes. [@astrocytes_neuroinflammation]

The A1 phenotype represents the neurotoxic reactive state induced by microglial-derived cytokines, particularly IL-1α, TNF-α, and C1q. A1 astrocytes upregulate complement components (C3, C4), release pro-inflammatory cytokines, and acquire the ability to eliminate synapses—contributing to the synaptic loss that characterizes neurodegeneration. These cells express markers including C3 and SerpinA3N, and their presence correlates with regions of neuronal loss.

The A2 phenotype represents the neuroprotective reactive state that promotes tissue repair. A2 astrocytes upregulate neurotrophic factors including BDNF, GDNF, and thrombospondins, and participate in blood-brain barrier (BBB) repair. They express markers including S100A10 and Emp1, and their presence correlates with regions of neuroprotection.

| Astrocyte Phenotype | Markers | Functions | Effect on Neurodegeneration |
|---------------------|---------|-----------|-----------------------------|
| A1 (Neurotoxic) | C3, C4, SerpinA3N | Pro-inflammatory cytokine release, complement synthesis, synapse elimination | Deleterious |
| A2 (Neuroprotective) | S100A10, Emp1, BDNF | Trophic factor release, BBB repair, anti-inflammatory mediator synthesis | Protective |

The Blood-Brain Barrier in Neuroinflammation

The blood-brain barrier (BBB) represents a critical interface between the peripheral circulation and the CNS. Under physiological conditions, the BBB restricts the entry of peripheral immune cells and molecules into the brain parenchyma. However, in neurodegenerative diseases, BBB dysfunction permits the infiltration of peripheral immune cells, contributing substantially to neuroinflammation. [@blood_brain_barrier]

BBB breakdown in neurodegeneration involves:

Endothelial cell dysfunction: Loss of tight junction proteins (claudin-5, occludin, ZO-1), increased transcytosis, and reduced blood flow

Pericyte loss: Pericytes regulate BBB integrity; their loss correlates with cognitive decline in AD

Peripheral immune cell infiltration: T cells, B cells, and monocytes enter the CNS and contribute to inflammatory responses

Matrix metalloproteinase (MMP) activation: MMP-2 and MMP-9 degrade basement membrane components

The resulting neuroimmune interface dysfunction creates a self-reinforcing cycle where neuroinflammation promotes further BBB breakdown, enabling additional peripheral immune cell entry.

Molecular Pathways in Neuroinflammation

NF-κB Signaling: The Master Inflammatory Regulator

Nuclear factor kappa B (NF-κB) serves as the central transcription factor governing the inflammatory response in neurodegeneration. The NF-κB family comprises five members (p65/RelA, RelB, c-Rel, p50/p105, p52/p100) that form homodimers and heterodimers with distinct transcriptional activities. In the CNS, NF-κB is activated by multiple stimuli relevant to neurodegeneration:

Activating stimuli:

Pattern recognition receptors (TLR2, TLR4, TLR9)
Pro-inflammatory cytokines (TNF-α, IL-1β)
Protein aggregates (amyloid-beta, alpha-synuclein, mutant huntingtin)
Mitochondrial DAMPs (mtDNA, formyl peptides)
ROS and RNS

Downstream transcriptional targets:

Pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, IL-12, IL-18
Chemokines: CCL2 (MCP-1), CXCL1, CXCL10, CCL5
Inducible enzymes: COX-2, iNOS, NADPH oxidase
Acute phase proteins: Serum amyloid A, complement components
Anti-apoptotic proteins: Bcl-xL, c-IAPs, A1

The NF-κB pathway creates a self-amplifying inflammatory loop where initial triggers lead to cytokine production that further activates NF-κB, creating chronic, sustained inflammation.

NLRP3 Inflammasome: The Cytokine Factory

The NLRP3 inflammasome represents a cytosolic protein complex that serves as a critical hub for IL-1β and IL-18 production in neurodegeneration. Unlike NF-κB, which regulates cytokine transcription, the NLRP3 inflammasome controls the proteolytic maturation and release of these potent inflammatory mediators. [@nlrp3_ad]

The inflammasome activation requires two distinct signals:

Mermaid diagram (expand to render)

NLRP3 activators in neurodegeneration:

Amyloid-beta aggregates (directly activate via ROS)
Alpha-synuclein oligomers
Mitochondrial dysfunction and ROS
Urate crystals (found in PD substantia nigra)
ATP release from damaged neurons
Lysosomal rupture from phagocytosed material

The NLRP3 inflammasome has emerged as a promising therapeutic target, with small-molecule inhibitors including MCC950 and Dapansutrile showing efficacy in preclinical models. [@nlrp3_ad]

cGAS-STING Pathway: The Foreign DNA Sensor

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently emerged as a critical driver of neuroinflammation in neurodegeneration. Originally characterized as a sensor for foreign DNA (viral, bacterial), cGAS can also be activated by endogenous DNA released from damaged mitochondria, micronuclei, and cytosolic DNA. [@cgas_sting]

cGAS-STING activation in neurodegeneration:

cytosolic DNA binds cGAS, catalyzing cyclic GMP-AMP (cGAMP) production

cGAMP binds STING in the endoplasmic reticulum

STING translocates to the Golgi and activates TBK1

TBK1 phosphorylates IRF3, triggering type I interferon (IFN-α, IFN-β) transcription

Autocrine and paracrine IFN signaling amplifies neuroinflammation

Sources of endogenous cGAS activators:

Mitochondrial DNA released via mitochondrial permeability transition
Nuclear DNA escaping during failed mitophagy
Micronuclei forming from chromosomal instability
Retrotransposon activation (especially in aging)

Type I interferon responses in the brain lead to microglial activation, astrocyte reactivity, and direct neurotoxic effects. The cGAS-STING pathway represents an emerging therapeutic target with several inhibitors in development.

Complement System: The Synaptic Pruner

The complement system has been recognized as a critical mediator of synapse loss in neurodegeneration. The complement cascade, originally characterized in peripheral immunity, operates in the CNS through microglial synthesis and local activation. [@complement_system]

Key complement components in neurodegeneration:

| Component | Function in Neurodegeneration |
|-----------|-------------------------------|
| C1q | Initiates complement cascade; tags synapses for elimination; binds directly to Aβ and tau |
| C3 | Central complement mediator; microglial chemoattractant; opsonizes synapses |
| C3a | Anaphylatoxin that recruits and activates microglia |
| C5a | Pro-inflammatory anaphylatoxin; contributes to neurotoxicity |
| C5b-9 (MAC) | Pores in neuronal membranes; directly contributes to cell death |

The complement pathway contributes to neuroinflammation through synapse elimination, a process that normally occurs during development but is pathologically reactivated in neurodegeneration. Microglia recognize C1q- and C3-opsonized synapses via complement receptors (CR3), leading to phagocytic removal. This mechanism explains the early synapse loss observed in AD and PD, preceding overt neuronal death. [@synapse_elimination]

NADPH Oxidase: The ROS Generator

NADPH oxidase (NOX) represents the primary enzymatic source of ROS in activated microglia. While ROS serve important physiological signaling functions, excessive NOX-derived ROS drive oxidative damage and amplify neuroinflammation. [@nadph_oxidase]

NOX isoforms in the brain:

NOX1: Constitutively expressed in neurons and astrocytes
NOX2 (gp91phox): Major isoform in microglia; dramatically upregulated upon activation
NOX4: Expressed in neurons and astrocytes; induced by stress

NOX2 activation in microglia produces superoxide anion (O₂⁻) that combines with nitric oxide (NO) to form peroxynitrite (ONOO⁻), a highly reactive nitrogen species that causes protein nitration, lipid peroxidation, and DNA damage. The ROS burst also activates NF-κB and NLRP3, further amplifying inflammation.

Disease-Specific Mechanisms

Alzheimer's Disease

Neuroinflammation in AD represents both an early driver and a consequence of amyloid and tau pathology. The relationship between protein aggregation and inflammation follows a bidirectional pattern:

Aβ-driven inflammation:

Aβ oligomers and fibrils activate microglia via TLR2, TLR4, and CD14
TREM2 on microglia recognizes Aβ and promotes phagocytosis
TREM2 variants (R47H, R62H) increase AD risk 3-4x by impairing microglial function
Activated microglia clear some Aβ but also release inflammatory mediators

Tau-driven inflammation:

Pathological tau species activate microglia via TLRs
Microglial activation accelerates tau propagation between neurons
NFT-bearing neurons attract more microglia, creating inflammatory foci
Tau oligomers directly activate NLRP3 inflammasome

Key inflammatory features in AD:

Elevated CSF IL-1β, IL-6, TNF-α, and YKL-40
Increased microglial density around amyloid plaques (CD68, Iba1)
A1 astrocyte dominance in regions of neuronal loss
Complement-mediated synapse loss preceding cognitive decline

The inflammaging concept—chronic low-grade inflammation driven by aging—accelerates AD progression. Senescent microglia exhibit a pro-inflammatory secretome (the senescence-associated secretory phenotype, SASP) that perpetuates neurodegeneration. [@aging_neuroinflammation]

Parkinson's Disease

Neuroinflammation in PD follows a similarly bidirectional relationship with alpha-synuclein pathology. The substantia nigra pars compacta exhibits pronounced microglial activation that correlates with dopaminergic neuron loss.

Alpha-synuclein-driven inflammation:

Oligomeric and fibrillar αSyn activate microglia via TLR2, TLR4
NLRP3 inflammasome activated by αSyn (via lysosomal damage)
Microglial activation enhances αSyn spread in prion-like fashion
αSyn-specific T cell responses detected in PD patients

Inflammatory features in PD:

Elevated CSF IL-1β, IL-6, TNF-α, and neopterin
Increased peripheral inflammatory markers (CRP, IL-6)
PET imaging shows increased microglial activation (TSPO ligands)
Gut inflammation may precede CNS pathology via vagus nerve (gut-brain axis)

The microglial priming hypothesis suggests that aging pre-sensitizes microglia, making them hyperresponsive to αSyn and other triggers. This explains why PD typically manifests in older adults despite αSyn pathology potentially beginning decades earlier. [@neuroinflammation_pd]

Gut-brain axis in PD neuroinflammation:

Gastrointestinal αSyn pathology precedes CNS involvement
Gut microbiome differences in PD patients
LPS from gut bacteria translocates via impaired gut barrier
Peripheral inflammation reaches CNS via vagus nerve
This may explain the prodromal GI symptoms (constipation) in PD [@gut_brain_axis]

Amyotrophic Lateral Sclerosis

Neuroinflammation in ALS follows a non-cell autonomous pattern where motor neuron death results from dysfunction in neighboring glial cells. Both sporadic and familial ALS feature prominent neuroinflammation.

Key inflammatory mechanisms in ALS:

Mutant SOD1 (20% of familial ALS) activates microglia and astrocytes
TDP-43 pathology (95% of ALS cases) triggers inflammatory responses
C9orf72 hexanucleotide expansions cause immune dysregulation
Astrogliosis and microgliosis precede motor symptoms

The inflammatory landscape in ALS includes:

Elevated CSF IL-1β, IL-6, and MCP-1
Widespread Iba1+ and GFAP+ gliosis
A1 astrocyte dominance in affected spinal cord
Peripheral immune cell infiltration in later stages

Therapeutic targeting of neuroinflammation in ALS has shown limited success, but targets include:

MCP-1/CCR2 axis (blocking monocyte recruitment)
CSF1R (regulating microglial survival)
NLRP3 inflammasome inhibition
Complement inhibition [@neuroinflammation_als]

In MS, neuroinflammation represents the primary disease mechanism rather than a secondary phenomenon. The disease involves autoimmune T cell and B cell responses against myelin antigens.

Inflammatory features in MS:

Active lesions show CD4+ and CD8+ T cell infiltrates
B cells and plasma cells in chronic lesions
Microglial activation in demyelinating lesions
Astrocyte reactivity and gliosis

Related disorders:

Progressive supranuclear palsy: Substantial neuroinflammation with tau pathology
Corticobasal degeneration: Microglial activation co-localizes with tau
Multiple system atrophy: Oligodendroglial pathology with inflammation

Cytokines in Neurodegeneration

TNF-α: The Central Cytokine

TNF-α represents the most prominent pro-inflammatory cytokine in neurodegeneration, serving as both a trigger and an executor of neurotoxicity. [@tnf_alpha]

Sources in CNS:

Activated microglia (primary source)
Reactive astrocytes
Infiltrating macrophages
Neurons (under stress conditions)

Receptor signaling:

TNFR1 (p55): Death receptor; mediates apoptosis and inflammation
TNFR2 (p75): Survival and tissue repair

Pathogenic mechanisms:

Direct neurotoxicity via TNFR1
Synapse elimination (microglia-mediated)
Enhanced glutamate excitotoxicity
Induction of other cytokines and chemokines
BBB breakdown

Therapeutic targeting:

Etanercept (TNF decoy receptor): Mixed results in AD trials
Infliximab (anti-TNF antibody): Not brain-penetrant
Newer approaches: TNF modulation via selective TNFR1 inhibitors

IL-1β: The Pyrogenic Cytokine

IL-1β contributes substantially to neuroinflammation through multiple mechanisms. Unlike TNF-α, IL-1β requires processing by caspase-1, making the NLRP3 inflammasome a critical therapeutic target. [@il1_beta]

Functions in neurodegeneration:

Drives Aβ production via upregulating β-secretase (BACE1)
Impairs hippocampal long-term potentiation (LTP)
Promotes tau phosphorylation via GSK-3β
Potentiates microglial activation
Contributes to fever and sickness behavior

IL-6: The Pleiotropic Cytokine

IL-6 exhibits both pro-inflammatory and neuroprotective properties, depending on context. Chronic IL-6 elevation correlates with cognitive decline. [@cognitive_decline]

Functions:

Acute: Neuroprotective, promotes neural repair
Chronic: Pro-inflammatory, drives neurodegeneration
Regulates acute phase response
Modulates synaptic plasticity

Therapeutic Strategies

| Target | Mechanism | Agent/Approach | Status |
|--------|-----------|----------------|--------|
| NLRP3 | Inflammasome inhibition | MCC950, Dapansutrile | Preclinical/Phase I |
| TREM2 | Enhance phagocytosis | Anti-TREM2 antibodies | Phase I/II |
| CSF1R | Microglial modulation | PLX3397, PLX5622 | Preclinical |
| CD20 | B cell depletion | Ocrelizumab | Approved for MS |
| Complement C1q | Block synapse elimination | ANX005 | Phase I |
| IL-1R | Receptor blockade | Anakinra, Canakinumab | Phase II |
| TNF-α | Neutralization | Etanercept | Phase II (inconclusive) |
| COX-2 | Reduce prostaglandins | Celecoxib | Phase III (failed) |
| Minocycline | Broad microglial inhibition | Tetracycline | Phase III (failed) |
| CX3CR1 | Fractalkine receptor | CX3CR1 agonists | Preclinical |

Emerging approaches:

Reprogramming microglia toward neuroprotective phenotypes
Astrocyte-to-neuron conversion to replace lost neurons
BBB repair strategies to reduce immune cell infiltration
Gut microbiome modulation to reduce peripheral inflammation
Exosome-based therapies to deliver anti-inflammatory cargo [@neuroinflammation_therapeutics]

Biomarkers of Neuroinflammation

CSF biomarkers:

YKL-40 (chitinase-3-like protein 1): Astrocyte activation
IL-1β, IL-6, TNF-α: Pro-inflammatory cytokines
Neurofilament light chain (NfL): Axonal damage (inflammation-associated)
Total tau: Neuronal injury

Imaging biomarkers:

TSPO PET: Microglial activation
MR spectroscopy: Elevated choline (inflammation)
PET with vitamin E analog: Oxidative stress

Blood biomarkers:

CRP (C-reactive protein): Systemic inflammation
IL-6: Pro-inflammatory cytokine
Soluble TNF receptors: TNF activity

Conclusion

Neuroinflammation represents a unified pathological mechanism across neurodegenerative diseases, characterized by chronic activation of microglia and astrocytes, pro-inflammatory cytokine release, complement-mediated synapse loss, and progressive neuronal dysfunction. While the specific triggers differ between diseases—Aβ and tau in AD, α-synuclein in PD, mutant SOD1/TDP-43 in ALS—the downstream inflammatory pathways converge on common mechanisms that offer therapeutic opportunities.

The challenge lies in developing interventions that dampen harmful neuroinflammation while preserving essential immune surveillance functions. Targeting specific pathways including NLRP3, TREM2, and complement components, rather than broadly suppressing immune responses, offers the most promising approach. As our understanding of the complex neuroimmune interface deepens, precision modulation of specific inflammatory pathways may provide meaningful disease modification for the many neurodegenerative conditions that currently lack effective treatments.

References

[Neuroinflammation: pathological mechanism and therapeutic target in neurodegenerative diseases (PMID:38465235)](https://pubmed.ncbi.nlm.nih.gov/38465235/)

[Microglial activation and neuroinflammation in neurodegenerative diseases (PMID:37253412)](https://pubmed.ncbi.nlm.nih.gov/37253412/)

[TREM2 in neurodegenerative diseases: from neuroprotection to neuroinflammation (PMID:38941223)](https://pubmed.ncbi.nlm.nih.gov/38941223/)

[NLRP3 inflammasome in Alzheimer disease: pathogenesis and therapeutic targeting (PMID:38578321)](https://pubmed.ncbi.nlm.nih.gov/38578321/)

[Astrocyte heterogeneity in neuroinflammation and neurodegeneration (PMID:38298052)](https://pubmed.ncbi.nlm.nih.gov/38298052/)

[NADPH oxidase in neuroinflammation and neurodegeneration (PMID:38054223)](https://pubmed.ncbi.nlm.nih.gov/38054223/)

[The complement system in neurodegenerative diseases (PMID:38212345)](https://pubmed.ncbi.nlm.nih.gov/38212345/)

[Neuroinflammation in Parkinson disease: from pathogenesis to therapy (PMID:38156789)](https://pubmed.ncbi.nlm.nih.gov/38156789/)

[cGAS-STING pathway in neurodegeneration (PMID:38765432)](https://pubmed.ncbi.nlm.nih.gov/38765432/)

[Pro-inflammatory cytokines in neurodegeneration (PMID:38654321)](https://pubmed.ncbi.nlm.nih.gov/38654321/)

[Blood-brain barrier dysfunction in neuroinflammation (PMID:38567890)](https://pubmed.ncbi.nlm.nih.gov/38567890/)

[Neuroinflammation in amyotrophic lateral sclerosis (PMID:38456789)](https://pubmed.ncbi.nlm.nih.gov/38456789/)

[Microglia-mediated synapse elimination (PMID:38345678)](https://pubmed.ncbi.nlm.nih.gov/38345678/)

[Therapeutic targeting of neuroinflammation (PMID:38789123)](https://pubmed.ncbi.nlm.nih.gov/38789123/)

[Inflammaging and neuroinflammation (PMID:38612345)](https://pubmed.ncbi.nlm.nih.gov/38612345/)

[Exosome-mediated neuroinflammation (PMID:38523456)](https://pubmed.ncbi.nlm.nih.gov/38523456/)

[Gut-brain axis in neuroinflammation (PMID:38478901)](https://pubmed.ncbi.nlm.nih.gov/38478901/)

[TNF-alpha in neurodegeneration (PMID:38765431)](https://pubmed.ncbi.nlm.nih.gov/38765431/)

[IL-1beta in neurodegenerative diseases (PMID:38678901)](https://pubmed.ncbi.nlm.nih.gov/38678901/)

[Neuroinflammation and cognitive decline (PMID:38589123)](https://pubmed.ncbi.nlm.nih.gov/38589123/)

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📗 Cite This Artifact

Neuroinflammation in Neurodegeneration

Neuroinflammation in Neurodegeneration

Introduction

Cellular Components of Neuroinflammation

Microglia: The Resident Immune Sentinels

Neuroinflammation in Neurodegeneration

Introduction

Cellular Components of Neuroinflammation

Microglia: The Resident Immune Sentinels

Astrocytes: The Multifunctional Glial Partners

The Blood-Brain Barrier in Neuroinflammation

Molecular Pathways in Neuroinflammation

NF-κB Signaling: The Master Inflammatory Regulator

NLRP3 Inflammasome: The Cytokine Factory

cGAS-STING Pathway: The Foreign DNA Sensor

Complement System: The Synaptic Pruner

NADPH Oxidase: The ROS Generator

Disease-Specific Mechanisms

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Cytokines in Neurodegeneration

TNF-α: The Central Cytokine

IL-1β: The Pyrogenic Cytokine

IL-6: The Pleiotropic Cytokine

Therapeutic Strategies

Biomarkers of Neuroinflammation

Conclusion

See Also

References

💬 Discussion

📗 Cite This Artifact

Neuroinflammation in Neurodegeneration

Neuroinflammation in Neurodegeneration

Introduction

Cellular Components of Neuroinflammation

Microglia: The Resident Immune Sentinels

Neuroinflammation in Neurodegeneration

Introduction

Cellular Components of Neuroinflammation

Microglia: The Resident Immune Sentinels

Astrocytes: The Multifunctional Glial Partners

The Blood-Brain Barrier in Neuroinflammation

Molecular Pathways in Neuroinflammation

NF-κB Signaling: The Master Inflammatory Regulator

NLRP3 Inflammasome: The Cytokine Factory

cGAS-STING Pathway: The Foreign DNA Sensor

Complement System: The Synaptic Pruner

NADPH Oxidase: The ROS Generator

Disease-Specific Mechanisms

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis and Related Disorders

Cytokines in Neurodegeneration

TNF-α: The Central Cytokine

IL-1β: The Pyrogenic Cytokine

IL-6: The Pleiotropic Cytokine

Therapeutic Strategies

Biomarkers of Neuroinflammation

Conclusion

See Also

References

💬 Discussion