Mitochondrial dysfunction and traffic jams in amyotrophic lateral sclerosis

Neurodegenerative diseases are characterized by progressive neuronal loss anatomically or physiologically and accumulation of protein in the cells. Mitochondria provide energy to these neuronal cells consuming 20% of the body's oxygen. Mitochondria are the dynamic membrane-bound cell organelles that function to generate ATP, regulate calcium homeostasis, and produce reactive oxygen species. Because of alterations in the electron transport chain, mutation, and environmental toxins, there is reduced ATP production, calcium dyshomeostasis, and increased oxidative stress, resulting in mitochondrial dysfunction, leading to the pathogenesis of neurodegenerative diseases such as ALS. ALS is described as the loss of upper and lower motor neurons resulting in progressive muscle denervation and loss of voluntary movements. There are multiple shreds of evidence in the literature regarding the mechanism involved in mitochondrial dysfunction and possible therapeutic targets to treat the condition. Moreover, different studies reported the role of different gene mutations and malfunctions in transport system responsible for the accumulation and aggregation of the proteins inside the brain cells. This accumulation and/or aggregation of proteins in the neuronal cells is known as neuronal traffic jam, which also plays the leading role in the progressive neurodegenerative diseases. In this review, we have elucidated the critical insights into mitochondrial dysfunction and neuronal traffic jam; and its role in the initiation and progression of ALS. Moreover, the pharmacological targets and possible conducts to this scenario are also brought together.