The role of the PLA2G6 gene in neurodegenerative diseases.

Xinyue Deng, Lamei Yuan, Joseph Jankovic, Hao Deng

Journal: Ageing research reviews 2023;89():101957

PMID: 37236368

Full Text on Elsevier Science View on PubMed

Abstract

PLA2G6-associated neurodegeneration (PLAN) represents a continuum of clinically and genetically heterogeneous neurodegenerative disorders with overlapping features. Usually, it encompasses three autosomal recessive diseases, including infantile neuroaxonal dystrophy or neurodegeneration with brain iron accumulation (NBIA) 2A, atypical neuronal dystrophy with childhood-onset or NBIA2B, and adult-onset dystonia-parkinsonism form named PARK14, and possibly a certain subtype of hereditary spastic paraplegia. PLAN is caused by variants in the phospholipase A2 group VI gene (PLA2G6), which encodes an enzyme involved in membrane homeostasis, signal transduction, mitochondrial dysfunction, and α-synuclein aggregation. In this review, we discuss PLA2G6 gene structure and protein, functional findings, genetic deficiency models, various PLAN disease phenotypes, and study strategies in the future. Our primary aim is to provide an overview of genotype-phenotype correlations of PLAN subtypes and speculate on the role of PLA2G6 in potential mechanisms underlying these conditions.

Address: Health Management Center, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.; Health Management Center, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Disease Genome Research Center, Central South University, Changsha 410013, Hunan, China.; Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030-4202, USA.; Health Management Center, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China; Disease Genome Research Center, Central South University, Changsha 410013, Hunan, China. Electronic address: [email protected].

DOI: 10.1016/j.arr.2023.101957

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MeSH Terms: Parkinsonian Disorders, Neuroaxonal Dystrophies, Group VI Phospholipases A2, Neurodegenerative Diseases, Genetic Association Studies, Dystonic Disorders, Mutation, Humans