Neuroinflammation: Cause, Consequence, or Therapeutic Target in Chronic Neurodegeneration — A Perspective

Abstract

Neuroinflammation — the sustained activation of central nervous system (CNS) innate and adaptive immune responses — is increasingly recognized as a central, yet complex, component of chronic neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease). Rather than being purely reactive, inflammatory processes can precede clinical symptoms, interact bidirectionally with disease-specific proteinopathies, and alter disease trajectories. This Perspective synthesizes mechanistic and translational evidence supporting three non-mutually exclusive roles for neuroinflammation: (1) an upstream contributor to disease initiation; (2) an amplifier/consequence of ongoing neurodegeneration; and (3) a mutable therapeutic target whose success depends on timing, cellular specificity and patient stratification. We highlight key molecular mediators (inflammasomes, microglial and astrocytic phenotypes, innate immune receptors such as TREM2), summarize advances in imaging and fluid biomarkers, and propose a pragmatic roadmap for translating immunomodulatory strategies — from precision biomarker-guided trials to combinatorial therapies that preserve beneficial immune functions while limiting chronic toxicity.