Sigma-1受体在神经退行性疾病中的角色

Neurodegenerative diseases are a type of diseases that mainly affect the neurons, such as dementia, amyotrophic lateral sclerosis, etc. Such diseases have brought great impact and burden to patients, families and the society, and it has always been a difficult problem to develop reasonable and effective treatments. Sigma-1 receptor is a non-opioid and non-G protein-coupled small molecule receptor which is abundantly expressed in the nervous system. It predominantly resides in the endoplasmic reticulum (ER), especially ER sub-region contacting mitochondria, namely the mitochondrial-associated membrane (MAM) in cell, and participates in a variety of important cell signaling pathways that affect cell survival. There are reports that multiple mutations of the Sigma-1 receptor are associated with the onset of neurodegenerative diseases. E102Q, as one of those mutations can cause juvenile amyotrophic lateral sclerosis. The absence of this receptor in animal models of neurodegenerative diseases can also aggravate the symptoms of the disease. In addition, agonists of this receptor have been shown to have neuroprotective effects. In this paper, we have introduced neurodegenerative diseases, mainly ALS and reviewed the function of Sigma-1 receptor and the possible pathogenic mechanism of its mutations, hoping to help and inspire the research and treatment of neurodegenerative diseases.