Peer-reviewed veterinary case report
Impaired mitochondrial calcium efflux contributes to disease progression in models of Alzheimer's disease.
- Journal:
- Nature communications
- Year:
- 2019
- Authors:
- Jadiya, Pooja et al.
- Affiliation:
- Department of Pharmacology · United States
- Species:
- rodent
Abstract
Impairments in neuronal intracellular calcium (Ca) handling may contribute to Alzheimer's disease (AD) development. Metabolic dysfunction and progressive neuronal loss are associated with AD progression, and mitochondrial calcium (Ca) signaling is a key regulator of both of these processes. Here, we report remodeling of theCaexchange machinery in the prefrontal cortex of individuals with AD. In the 3xTg-AD mouse model impairedCaefflux capacity precedes neuropathology. Neuronal deletion of the mitochondrial Na/Caexchanger (NCLX, Slc8b1 gene) accelerated memory decline and increased amyloidosis and tau pathology. Further, genetic rescue of neuronal NCLX in 3xTg-AD mice is sufficient to impede AD-associated pathology and memory loss. We show thatCaoverload contributes to AD progression by promoting superoxide generation, metabolic dysfunction and neuronal cell death. These results provide a link between the calcium dysregulation and metabolic dysfunction hypotheses of AD and suggestCaexchange as potential therapeutic target in AD.
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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/31467276/