Loading
Life sciences · Journal article
European Journal of Neuroscience · November 1, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
ABSTRACT Brain aging is the principal risk factor for both neurodegenerative diseases (NDDs) and cerebral ischemic disorders, yet the subcellular mechanisms linking these conditions remain incompletely defined. Mitochondria‐associated membranes (MAMs)—specialized contact sites between the endoplasmic reticulum (ER) and mitochondria—sit at the intersection of two well‐established hallmarks of aging, mitochondrial dysfunction, and loss of proteostasis, making them an attractive mechanistic node for understanding age‐related brain decline. In this review, we propose a MAM‐centered framework that unifies neurodegenerative and ischemic brain pathology under the broader paradigm of brain aging. We first summarize the molecular architecture of MAMs and their core functions in neuronal Ca 2+ transfer, mitochondrial dynamics, lipid metabolism, inflammasome assembly, and autophagic quality control, together with emerging evidence from non‐neuronal brain cells. We then examine how MAM dysfunction intersects with five hallmarks of aging—mitochondrial dysfunction, loss of proteostasis, disabled macroautophagy, chronic inflammation (inflammaging), and altered intercellular communication—drawing on evidence from physiological aging and cellular senescence models. Next, we discuss disease‐specific roles of MAMs in cerebral ischemia and in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. A central theme emerges: Rather than a unidirectional decline of MAMs, brain aging is associated with a loss of MAM homeostasis, in which both insufficient and excessive ER–mitochondria coupling can be pathological and the shared deficit is the failure to maintain contact‐site function within an optimal range. Finally, we consider age‐relevant therapeutic and biomarker strategies targeting MAMs and their potential translation into geriatric neurology. To our knowledge, this is the first review to integrate MAM biology across physiological brain aging, cerebral ischemia, and the four major NDDs within a single homeostatic framework, offering a unified perspective on the mechanisms of age‐related brain decline.