Work

The metabolic crossroads: glycolysis in cancer and neurodegeneration

Year: 2025

Type: article

Abstract: BACKGROUND: Emerging epidemiological data reveal a compelling inverse relationship between cancer and neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). The biological mechanisms underlying this paradox remain unclear. The aim of this study was to identify shared metabolic pathways that may mediate this inverse association. METHODS: We integrated single-cell and bulk RNA sequencing data from TCGA and GEO databases to examine metabolic alterations in colon adenocarcinoma (COAD) and PD. Furthermore, we validated the expression of the critical gene in human tissue samples using immunohistochemistry and corroborated its functional roles through in vitro experimental assays. RESULTS: Divergent regulation of glycolysis was observed between COAD and PD. A key finding was the upregulation of acetyl-CoA acyltransferase 2 (ACAA2) in PD and, more markedly, in AD, contrasting with its frequent downregulation in cancers. Functionally, ACAA2 overexpression has been demonstrated to inhibit glycolysis and inflammation in colorectal cancer and neurological models. CONCLUSIONS: Our findings identify glycolysis as a shared but oppositely regulated pathway linking cancer and neurodegeneration. ACAA2 may serve as a molecular mediator of this metabolic divergence, offering new insights into disease crosstalk and potential therapeutic targets.

Source: BMC Neurology

DOI: 10.1186/s12883-025-04533-6

Authors: Shaopeng Zeng, Huan Liu, Shilong Han, Jun Chen, Ying Yang, Jing Zhang

Institutions: First Affiliated Hospital Zhejiang University, Zhejiang University

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,090