The interplay between metabolic homeostasis and neurodegeneration: insights into the neurometabolic nature of amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that is characterized by the selective degeneration of upper motor neurons and lower spinal motor neurons, resulting in the progressive paralysis of all voluntary muscles. Approximately 10 % of ALS cases are linked to known genetic mutations, with the remaining 90 % of cases being sporadic. While the primary pathology in ALS is the selective death of upper and lower motor neurons, numerous studies indicate that an imbalance in whole body and/or cellular metabolism influences the rate of progression of disease. This review summarizes current research surrounding the impact of impaired metabolic physiology in ALS. We extend ideas to consider prospects that lie ahead in terms of how metabolic alterations may impact the selective degeneration of neurons in ALS and how targeting of adenosine triphosphate-sensitive potassium (K_ATP) channels may represent a promising approach for obtaining neuroprotection in ALS.