Alzheimer's disease (AD) is a multifactorial neurodegenerative pathology characterized by a progressive decline of cognitive functions. Alteration of various signaling cascades affecting distinct subcellular compartment functions and their communication likely contribute to AD progression. Among others, the alteration of the physical association between the endoplasmic reticulum (ER) and mitochondria, also reffered as mitochondria-associated membranes (MAMs), impacts various cellular housekeeping functions such as phospholipids-, glucose-, cholesterol-, and fatty-acid-metabolism, as well as calcium signaling, which are all altered in AD. Our review describes the physical and functional proteome crosstalk between the ER and mitochondria and highlights the contribution of distinct molecular components of MAMs to mitochondrial and ER dysfunctions in AD progression. We also discuss potential strategies targeting MAMs to improve mitochondria and ER functions in AD.
Keywords: APOE; APP-C-terminal fragments (APP-CTFs); Alzheimer’s disease (AD); Amyloid β peptide (Aβ); Endoplasmic Reticulum (ER); Mitochondria-Associated Membranes (MAMs); Unfolded Protein Response (UPR); calcium signaling; cholesterol; fatty acid; lipids; mitochondria; phospholipids; tau; unfolded protein response; β amyloid precursor protein (APP).