Stable ATP Levels: A New Strategy to Prevent Neurodegenerative Diseases

Abnormal accumulation of toxic proteins is a hallmark of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. A yeast study published in eLife uncovers a key link between cellular energy metabolism and protein clumping, offering fresh insights for disease treatment.

Researchers used fluorescent imaging to track real-time ATP changes in single cells. They found AMPK kinase works together with adenylate kinase ADK and purine synthesis regulator Bas1 to sustain steady intracellular ATP concentrations. If this regulatory system malfunctions, cells suffer sudden, short-term ATP drops. Such brief energy deficiency directly triggers abnormal aggregation of toxic proteins including α-synuclein and mutant huntingtin fragments, leading to severe cellular toxicity. On the contrary, boosting cellular ATP reserves effectively reduces protein deposits, with proteasomes acting as the main cleanup machinery.

Traditional biochemical tests only measure average ATP levels across cell populations and fail to capture fleeting ATP crashes. Single-cell imaging clearly proves the causal link between sudden energy loss and protein aggregation.This research establishes a connection between energy homeostasis and proteostasis. AMPK activators like metformin have shown promising effects in animal disease models. Sustaining stable intracellular ATP may pave the way for more effective neuroprotective therapies in the future.

FOR DETAIL:  https://doi.org/10.7554/eLife.67659

Article from: