This study looks at the effect of genetically disrupting circadian rhythms on neurodegeneration, and finds functional ties between the two.
Krishnan N, Rakshit K, Chow ES, Wentzell JS, Kretzschmar D, Giebultowicz JM. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants. Neurobiol Dis. 2012 Mar;45(3):1129-35. PubMed PMID: 22227001; PubMed Central PMCID: PMC3291167.
Mutations in swi and sws are used in the study to model neurodegeneration.
The swi gene appears not to have been well conserved (no strong-scoring matches at DIOPT for example). By contrast, the sws gene has been conserved. The fly sws gene is related to the human gene PNPLA6 (also called NTE; Entrez Gene ID 10908). PNPLA6 is associated with spastic paraplegia 39, one of a group of spastic paraplegias. According to the literature summary at Entrez Gene, the normal role of the PNPLA6 protein is as a phopholipase that deacetyates intracellular phophatidylcholine, producing glycerophophocholine.
Mutations in per are used in the study to disrupt circadian rhythms.
The fly per gene has at least 3 putative orthologs in the human genome, PER1, PER2 and PER3. According to OMIM, mutations in PER2 are associated with familial advanced sleep phase syndrome.
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