Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis.

Suwarna Chakraborty, Sunil Jamuna Tripathi, Edwin Vázquez-Rosa, Kalyani Chaubey, Hisashi Fujioka, Emiko Miller, Richa Tyagi, Thibaut Vignane, Sudarshana M Sharma, Bobby Thomas, Zachary M Weil, Randy J Nelson, Milos R Filipovic, Benjamin C Orsburn, Solomon H Snyder, Andrew A Pieper, Bindu D Paul

Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.Department of Physiology, Pharmacology, & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205. · pubmed

Paper

Abstract

Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen sulfide production, is dysregulated in aging and neurodegenerative diseases including Alzheimer's disease and Huntington's disease, both marked by cognitive decline in addition to motor deficits. To determine whether CSE loss directly causes cognitive decline, we genetically ablated CSE in mice. This loss was sufficient to induce oxidative damage, compromise blood-brain barrier integrity, impair neurogenesis and neurotrophin signaling, and elicit cognitive deficits. Global proteomic analysis further revealed molecular alterations that contribute to impaired neurogenesis. Our findings establish CSE as an essential guardian of homeostatic brain health and identify it as a potential therapeutic target for neurodegenerative disorders.

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Research summary

Cystathionine γ-lyase is essential for maintaining cognitive function and neurogenesis, and its loss leads to cognitive decline. The study addresses a potential root cause of cognitive decline associated with aging and neurodegenerative diseases, making it relevant to longevity research.

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