Cell Membrane Dysfunction in the Pathophysiology of Neurological Disorders

Neuronal cell membranes are dynamic lipid–protein assemblies essential for ion homeostasis, neurotransmission, and cellular integrity. Disruption of membrane composition and function has emerged as a unifying pathological mechanism across diverse neurological disorders; however, the molecular links between specific membrane defects and disease progression remain incompletely understood. This review systematically examines four major axes of membrane dysfunction in the central nervous system: (۱) lipid dysregulation—including phospholipid imbalance, sphingolipid accumulation, and aberrant cholesterol metabolism—and its downstream effects on neuroinflammation and oxidative stress; (۲) α-synuclein–membrane interactions in Parkinson’s disease, wherein oligomeric species form pore-like structures that permeabilize lipid bilayers and drive dopaminergic neurodegeneration; (۳) mitochondrial membrane damage leading to cytosolic mtDNA leakage, which activates cGAS–STING signaling and inflammasome-mediated chronic neuroinflammation; and (۴) blood–brain barrier impairment, through which dysregulated aquaporin channels and disrupted tight junctions promote vasogenic edema and epileptogenesis. Furthermore, we discuss biomimetic membrane-based nanomaterials as emerging theranostic platforms capable of crossing the BBB for targeted drug delivery and molecular imaging. Collectively, these findings underscore membrane integrity as a critical determinant of neuronal survival and highlight membrane-targeted interventions as a promising frontier in neurological disease therapy

کلیدواژه ها:

Cell membrane dysfunction ، lipid dysregulation ، neuroinflammation ، blood–brain barrier ، Parkinson’s disease ، biomimetic nanomaterials