Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Traxler L
PROVIDER: S-EPMC9458870 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer's disease.
Traxler Larissa L Herdy Joseph R JR Stefanoni Davide D Eichhorner Sophie S Pelucchi Silvia S Szücs Attila A Santagostino Alice A Kim Yongsung Y Agarwal Ravi K RK Schlachetzki Johannes C M JCM Glass Christopher K CK Lagerwall Jessica J Galasko Douglas D Gage Fred H FH D'Alessandro Angelo A Mertens Jerome J
Cell metabolism 20220819 9
The drivers of sporadic Alzheimer's disease (AD) remain incompletely understood. Utilizing directly converted induced neurons (iNs) from AD-patient-derived fibroblasts, we identified a metabolic switch to aerobic glycolysis in AD iNs. Pathological isoform switching of the glycolytic enzyme pyruvate kinase M (PKM) toward the cancer-associated PKM2 isoform conferred metabolic and transcriptional changes in AD iNs. These alterations occurred via PKM2's lack of metabolic activity and via nuclear tra ...[more]
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