Mitochondria-associated membranes: A hub for neurodegenerative diseases

In eukaryotic cells, organelles could coordinate complex mechanisms of signaling transduction metabolism and gene expression through their functional interactions. The functional domain between ER and mitochondria, called mitochondria-associated membranes (MAM), is closely associated with various physiological functions including intracellular lipid transport, Ca²⁺ transfer, mitochondria function maintenance, and autophagosome formation. In addition, more evidence suggests that MAM modulate cellular functions in health and disease. Studies have also demonstrated the association of MAM with numerous diseases, including neurodegenerative diseases, cancer, viral infection, obesity, and diabetes. In fact, recent evidence revealed a close relationship of MAM with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases. In this view, elucidating the role of MAM in neurodegenerative diseases is particularly important. This review will focus the main tethering protein complexes of MAM and functions of MAM. Besides, the role of MAM in the regulation of neurodegenerative diseases and the potential molecular mechanisms is introduced to provide a new understanding of the pathogenesis of these diseases.