There's Something Wrong with my MAM; the ER–Mitochondria Axis and Neurodegenerative Diseases

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no cures. All are characterised by damage to several seemingly disparate cellular processes. The broad nature of this damage makes understanding pathogenic mechanisms and devising new treatments difficult. Can the different damaged functions be linked together in a common disease pathway and which damaged function should be targeted for therapy? Many functions damaged in neurodegenerative diseases are regulated by communications that mitochondria make with a specialised region of the endoplasmic reticulum (ER; mitochondria-associated ER membranes or 'MAM'). Moreover, several recent studies have shown that disturbances to ER-mitochondria contacts occur in neurodegenerative diseases. Here, we review these findings.