In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 9 ( 2023-9-21), p. e1010893-
Abstract:
Brains are highly metabolically active organs, consuming 20% of a person’s energy at resting state. A decline in glucose metabolism is a common feature across a number of neurodegenerative diseases. Another common feature is the progressive accumulation of insoluble protein deposits, it’s unclear if the two are linked. Glucose metabolism in the brain is highly coupled between neurons and glia, with glucose taken up by glia and metabolised to lactate, which is then shuttled via transporters to neurons, where it is converted back to pyruvate and fed into the TCA cycle for ATP production. Monocarboxylates are also involved in signalling, and play broad ranging roles in brain homeostasis and metabolic reprogramming. However, the role of monocarboxylates in dementia has not been tested. Here, we find that increasing pyruvate import in Drosophila neurons by over-expression of the transporter bumpel , leads to a rescue of lifespan and behavioural phenotypes in fly models of both frontotemporal dementia and Alzheimer’s disease. The rescue is linked to a clearance of late stage autolysosomes, leading to degradation of toxic peptides associated with disease. We propose upregulation of pyruvate import into neurons as potentially a broad-scope therapeutic approach to increase neuronal autophagy, which could be beneficial for multiple dementias.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010893
DOI:
10.1371/journal.pgen.1010893.g001
DOI:
10.1371/journal.pgen.1010893.g002
DOI:
10.1371/journal.pgen.1010893.g003
DOI:
10.1371/journal.pgen.1010893.g004
DOI:
10.1371/journal.pgen.1010893.g005
DOI:
10.1371/journal.pgen.1010893.g006
DOI:
10.1371/journal.pgen.1010893.t001
DOI:
10.1371/journal.pgen.1010893.t002
DOI:
10.1371/journal.pgen.1010893.s001
DOI:
10.1371/journal.pgen.1010893.s002
DOI:
10.1371/journal.pgen.1010893.s003
DOI:
10.1371/journal.pgen.1010893.s004
DOI:
10.1371/journal.pgen.1010893.s005
DOI:
10.1371/journal.pgen.1010893.s006
DOI:
10.1371/journal.pgen.1010893.s007
DOI:
10.1371/journal.pgen.1010893.s008
DOI:
10.1371/journal.pgen.1010893.s009
DOI:
10.1371/journal.pgen.1010893.s010
DOI:
10.1371/journal.pgen.1010893.s011
DOI:
10.1371/journal.pgen.1010893.s012
DOI:
10.1371/journal.pgen.1010893.s013
DOI:
10.1371/journal.pgen.1010893.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
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