Редактирование: AFG3L2 (раздел)

==Publications==

{{medline-entry
|title=Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22045296
|abstract=Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested [[AFG3L2]] (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), [[MAT1A]], [[MAT2A]] (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), [[SYNJ1]] and [[SYNJ2]] (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in [[SYNJ2]], [[MAT1A]], [[AFG3L2]] and [[SYNJ1]] and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the [[SYNJ2]] association with cognitive abilities (lowest P=0.00077). [[SYNJ2]] is a novel gene in which variation is potentially associated with cognitive abilities.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Child
* Child, Preschool
* Cognition
* Cohort Studies
* Evolution, Molecular
* Female
* Genotype
* Humans
* Longevity
* Male
* Memory
* Middle Aged
* Nerve Tissue Proteins
* Phosphoric Monoester Hydrolases
* Polymorphism, Single Nucleotide
* Reproducibility of Results

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283186
}}
{{medline-entry
|title=Haploinsufficiency of [[AFG3L2]], the gene responsible for spinocerebellar ataxia type 28, causes mitochondria-mediated Purkinje cell dark degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19625515
|abstract=Paraplegin and [[AFG3L2]] are ubiquitous nuclear-encoded mitochondrial proteins that form hetero-oligomeric paraplegin-[[AFG3L2]] and homo-oligomeric [[AFG3L2]] complexes in the inner mitochondrial membrane, named m-AAA proteases. These complexes ensure protein quality control in the inner membrane, jointly with a chaperone-like activity on the respiratory chain complexes. Despite coassembling in the same complex, mutations of either paraplegin or [[AFG3L2]] cause two different neurodegenerative disorders. Indeed, mutations of paraplegin are responsible for a recessive form of hereditary spastic paraplegia, whereas mutations of [[AFG3L2]] have been recently associated to a dominant form of spinocerebellar ataxia (SCA28). In this work, we report that the mouse model haploinsufficient for Afg3l2 recapitulates important pathophysiological features of the human disease, thus representing the first SCA28 model. Furthermore, we propose a pathogenetic mechanism in which respiratory chain dysfunction and increased reactive oxygen species production caused by Afg3l2 haploinsufficiency lead to dark degeneration of Purkinje cells and cerebellar dysfunction.
|mesh-terms=* ATP-Dependent Proteases
* ATPases Associated with Diverse Cellular Activities
* Adenosine Triphosphatases
* Adenosine Triphosphate
* Aging
* Animals
* Apoptosis
* Cerebellum
* Disease Models, Animal
* Ganglia, Spinal
* Gliosis
* Mice
* Mice, Mutant Strains
* Mitochondria
* Motor Activity
* Motor Neurons
* Nerve Degeneration
* Purkinje Cells
* Reactive Oxygen Species
* Spinal Cord
* Spinocerebellar Ataxias

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6665556
}}