Dynamin-related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases.

Abstract

Mitochondria play a key role in the maintenance of neuronal function by continuously providing energy. Here, we will give a detailed review about the recent developments in regards to dynamin-related protein 1 (Drp1) induced unbalanced mitochondrial dynamics, excessive mitochondrial division, and neuronal injury in neural system dysfunctions and neurodegenerative diseases, including the Drp1 knockout induced mice embryonic death, the dysfunction of the Drp1-dependent mitochondrial division induced neuronal cell apoptosis and impaired neuronal axonal transportation, the abnormal interaction between Drp1 and amyloid β (Aβ) in Alzheimer's disease (AD), the mutant Huntingtin (Htt) in Huntington's disease (HD), and the Drp1-associated pathogenesis of other neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).Drp1 is required for mitochondrial division determining the size, shape, distribution, and remodeling as well as maintaining of mitochondrial integrity in mammalian cells. In addition, increasing reports indicate that the Drp1 is involved in some cellular events of neuronal cells causing some neural system dysfunctions and neurodegenerative diseases, including impaired mitochondrial dynamics, apoptosis, and several posttranslational modification induced increased mitochondrial divisions. Recent studies also revealed that the Drp1 can interact with Aβ, phosphorylated τ, and mutant Htt affecting the mitochondrial shape, size, distribution, axonal transportation, and energy production in the AD and HD neuronal cells. These changes can affect the health of mitochondria and the function of synapses causing neuronal injury and eventually leading to the dysfunction of memory, cognitive impairment, resting tremor, posture instability, involuntary movements, and progressive muscle atrophy and paralysis in patients.