The Role of Mitochondrial Genes in Neurodegenerative Disorders

Abstract

Mitochondrial disorders are clinically heterogeneous, resulting from nuclear gene and mitochondrial mutations that disturb the mitochondrial functions and dynamics. There is a lack of evidence linking mtDNA mutations to neurodegenerative disorders, mainly due to the absence of noticeable neuropathological lesions in postmortem samples. This review describes various gene mutations in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. These abnormalities, including PINK1, Parkin, and SOD1 mutations, seem to reveal mitochondrial dysfunctions due to either mtDNA mutation or deletion, the mechanism of which remains unclear in depth.

Keywords: Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; mtDNA; multiple sclerosis; neurodegeneration; stroke.

Fig. (1)

Schematic representation of mitochondrial structure and genome. D (Displacement) loop indicates the non-coding region, and the arrows represent the path of transcription of mtDNA; 12S and 16S RNA indicates the two ribosomal RNAs; MTND genes 1 and 2 represent ND genes 1 and 2 in combination with mitochondrial tRNA; COX1, COX2, COX3 represent cytochrome C oxidase subunits 1-3; ND3, ND4L, ND5, ND6 represent the subunits of NADH dehydrogenase, and CYTB represents the gene coding for cytochrome B. (A) mtDNA non-coding region: D loop; (B) Encoding of complex I, III, IV, V subunits. Complex I: MTND1, MTND2, ND3, ND4, ND4L, ND5, ND6. complex III: Cytochrome B. complex IV: COX1, COX2, COX3. complex V: ATPase 6 and ATPase 8.

Fig. (2)

Illustration of neurodegenerative diseases in association with mitochondrial dysfunction.