Mitochondrial Genes and Neurodegenerative Disease

Abstract

Mitochondrial dysfunction is increasingly recognised as a cause of neurodegeneration in both primary mitochondrial diseases and common neurodegenerative diseases, including Parkinson's, Alzheimer's and Huntington's diseases and amyotrophic lateral sclerosis (ALS).In this chapter, we will focus on the molecular basis of mitochondrial dysfunction and the mechanisms bridging it to neurodegeneration. In the fi rst part, we will summarise some basic concepts of mitochondrial biology. We will then cover paediatric diseases, including different types of encephalopathies, Leigh disease, leukoencephalopathies and a variety of syndromes with peculiar features. Finally, we will cover diseases in adults, including MNGIE disease, Friedreich ataxia and the disorders associated with alterations in mitochondrial dynamics and quality control. These include axonal Charcot-Marie-Tooth neuropathy, hereditary spastic paraplegia, and autosomal dominant optic atrophy, as well as the inherited and idiopathic forms of common neurodegenerative diseases.

Dictyostelium discoideum as a Model for Investigating Neurodegenerative Diseases

“…Because the brain has a high energy demand, mitochondrial function is critical to neuronal health (Han et al, 2021). Mitochondrial dysfunction has been observed in many neurodegenerative diseases including AD, PD, and ALS; however, it is unclear if mitochondrial dysfunction is a cause or byproduct of neurodegenerative diseases (Reddy and Beal, 2005;Manczak et al, 2006;Viscomi et al, 2016;Onyango et al, 2017;Pearce et al, 2019). In many familial neurodegenerative disease cases, mutant proteins such as Aβ in AD, parkin, DJ-1, and α-synuclein in PD, huntingtin in HD, and superoxide dismutase 1 (SOD1) in ALS can localize to the mitochondria.…”