ER-organelle contacts: A signaling hub for neurological diseases

Neuronal health is closely linked to the homeostasis of intracellular organelles, and organelle dysfunction affects the pathological progression of neurological diseases. In contrast to isolated cellular compartments, a growing number of studies have found that organelles are largely interdependent structures capable of communicating through membrane contact sites (MCSs). MCSs have been identified as key pathways mediating inter-organelle communication crosstalk in neurons, and their alterations have been linked to neurological disease pathology. The endoplasmic reticulum (ER) is a membrane-bound organelle capable of forming an extensive network of pools and tubules with important physiological functions within neurons. There are multiple MCSs between the ER and other organelles and the plasma membrane (PM), which regulate a variety of cellular processes. In this review, we focus on ER-organelle MCSs and their role in a variety of neurological diseases. We compared the biological effects between different tethering proteins and the effects of their respective disease counterparts. We also discuss how altered ER-organelle contacts may affect disease pathogenesis. Therefore, understanding the molecular mechanisms of ER-organelle MCSs in neuronal homeostasis will lay the foundation for the development of new therapies targeting ER-organelle contacts.