Neuroinflammation, Autophagy, and Neurodegeneration: Mechanisms and Therapeutic Insights

Apr 1, 2026CNS & neurological disorders drug targets

Brain Inflammation, Cell Cleanup, and Nerve Cell Damage: How They Work and Potential Treatments

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Neuroinflammation and autophagy dysregulation are critical in the pathogenesis of neurodegenerative diseases.

Neuroinflammation arises from a sustained immune response, leading to chronic production of pro-inflammatory cytokines and oxidative stress that can damage neurons.
Defective autophagy promotes the accumulation of proteins like amyloid-β, tau, and α-synuclein, which may worsen neuroinflammation.
Key regulatory pathways, such as mTOR and AMPK, are implicated in the interplay between neuroinflammation and autophagy dysfunction.
Novel therapeutic strategies, including mTOR inhibitors and autophagy enhancers, could help restore cellular balance.
Advanced technologies like CRISPR and RNA therapeutics may offer new ways to target molecular mechanisms in neurodegenerative disorders.

AI simplified

Neuroinflammation and autophagy dysregulation are critical in the pathogenesis of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's disease. Neuroinflammation occurs after a sustained immune response, which transitions into a chronic pathological state, leading to the sustained generation of pro-inflammatory cytokines and oxidative stress, causing neuronal damage. Meanwhile, defective autophagy exacerbates disease by promoting protein accumulation, e.g., amyloid-β, tau, and α-synuclein, thereby enhancing neuroinflammation. In this review, we focus on critical pathways, including mTOR and AMPK, that regulate these events and illustrate how their dysregulation may lead to a vicious cycle of inflammation and autophagy dysfunction. Novel therapeutic strategies, including mTOR inhibitors, autophagy enhancers, and inflammasome modulators, may contribute to cellular homeostasis. Furthermore, approaches that promote upregulation of chaperone- mediated autophagy can enable selective clearance of mediators of inflammatory response and aggregated/misfolded proteins. Advanced approaches such as CRISPR-based gene editing and RNA therapeutics provide tools to target molecular mechanisms involved in these neurodegenerative disorders, whereas the development of reliable biomarkers and novel delivery strategies may pave the way for personalized treatments. Moreover, artificial intelligence-based workflows and models may strengthen phenotypic and mechanistic screening of autophagy modulators and potential drug targets. By incorporating these forthcoming insights, this review underscores the critical need for comprehensive therapies that target both neuroinflammation and autophagy dysfunction to mitigate disease progression and improve patient outcomes.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗View full text ↗

Neuroinflammation, Autophagy, and Neurodegeneration: Mechanisms and Therapeutic Insights

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief