Physical activity, cathepsin B, and cognitive health

Qian Yu; Zhihao Zhang; Fabian Herold; Sebastian Ludyga; Jin Kuang; Yanxia Chen; Zijun Liu; Kirk I. Erickson; Bret H. Goodpaster; Boris Cheval; Dominika M. Pindus; Arthur F. Kramer; Charles H. Hillman; Teresa Liu-Ambrose; Keith W. Kelley; Hyo Youl Moon; Aiguo Chen; Liye Zou

doi:10.1016/j.molmed.2024.12.010

Physical activity, cathepsin B, and cognitive health

Qian Yu, Zhihao Zhang, Fabian Herold, Sebastian Ludyga, Jin Kuang, Yanxia Chen, Zijun Liu, Kirk I. Erickson, Bret H. Goodpaster, Boris Cheval, Dominika M. Pindus, Arthur F. Kramer, Charles H. Hillman, Teresa Liu-Ambrose, Keith W. Kelley, Hyo Youl Moon, Aiguo Chen, Liye Zou

Research output: Contribution to journal › Review article › peer-review

Abstract

Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) – a protease released by skeletal muscle during PA – acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.g., hippocampus and prefrontal cortex) that support performance in specific cognitive domains including memory, learning, and executive function. However, the evidence regarding the role of PA-induced changes in CTSB as a mediator of PA-induced cognitive health in humans is mixed. To guide future research, this article identifies key factors that may explain the observed heterogeneity in the findings from human studies and proposes a PA–CTSB–cognition model.

Original language	English (US)
Journal	Trends in Molecular Medicine
DOIs	https://doi.org/10.1016/j.molmed.2024.12.010
State	Accepted/In press - 2025

Keywords

brain health
cognition
CTSB
exercise
myokine

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology

Online availability

10.1016/j.molmed.2024.12.010

Cite this

Yu, Q., Zhang, Z., Herold, F., Ludyga, S., Kuang, J., Chen, Y., Liu, Z., Erickson, K. I., Goodpaster, B. H., Cheval, B., Pindus, D. M., Kramer, A. F., Hillman, C. H., Liu-Ambrose, T., Kelley, K. W., Moon, H. Y., Chen, A., & Zou, L. (Accepted/In press). Physical activity, cathepsin B, and cognitive health. Trends in Molecular Medicine. https://doi.org/10.1016/j.molmed.2024.12.010

@article{ccd33da2668a461b9aa34abac66e209f,

title = "Physical activity, cathepsin B, and cognitive health",

abstract = "Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) – a protease released by skeletal muscle during PA – acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.g., hippocampus and prefrontal cortex) that support performance in specific cognitive domains including memory, learning, and executive function. However, the evidence regarding the role of PA-induced changes in CTSB as a mediator of PA-induced cognitive health in humans is mixed. To guide future research, this article identifies key factors that may explain the observed heterogeneity in the findings from human studies and proposes a PA–CTSB–cognition model.",

keywords = "brain health, cognition, CTSB, exercise, myokine",

author = "Qian Yu and Zhihao Zhang and Fabian Herold and Sebastian Ludyga and Jin Kuang and Yanxia Chen and Zijun Liu and Erickson, {Kirk I.} and Goodpaster, {Bret H.} and Boris Cheval and Pindus, {Dominika M.} and Kramer, {Arthur F.} and Hillman, {Charles H.} and Teresa Liu-Ambrose and Kelley, {Keith W.} and Moon, {Hyo Youl} and Aiguo Chen and Liye Zou",

note = "This article was supported by Shenzhen Educational Research Funding (grant zdzb2014 ), the Shenzhen Science and Technology Innovation Commission ( 202307313000096 ), the Social Science Foundation from the China Ministry of Education ( 23YJA880093 ), a post-doctoral fellowship (2022M711174), the National Center for Mental Health ( Z014 ), the Research Excellence Scholarships of Shenzhen University ( ZYZD2305 ), and the Science and Technology Innovation Projects of the State General Administration of Sports ( 23KJCX057 ).",

year = "2025",

doi = "10.1016/j.molmed.2024.12.010",

language = "English (US)",

journal = "Trends in Molecular Medicine",

issn = "1471-4914",

publisher = "Elsevier Ltd",

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TY - JOUR

T1 - Physical activity, cathepsin B, and cognitive health

AU - Yu, Qian

AU - Zhang, Zhihao

AU - Herold, Fabian

AU - Ludyga, Sebastian

AU - Kuang, Jin

AU - Chen, Yanxia

AU - Liu, Zijun

AU - Erickson, Kirk I.

AU - Goodpaster, Bret H.

AU - Cheval, Boris

AU - Pindus, Dominika M.

AU - Kramer, Arthur F.

AU - Hillman, Charles H.

AU - Liu-Ambrose, Teresa

AU - Kelley, Keith W.

AU - Moon, Hyo Youl

AU - Chen, Aiguo

AU - Zou, Liye

N1 - This article was supported by Shenzhen Educational Research Funding (grant zdzb2014 ), the Shenzhen Science and Technology Innovation Commission ( 202307313000096 ), the Social Science Foundation from the China Ministry of Education ( 23YJA880093 ), a post-doctoral fellowship (2022M711174), the National Center for Mental Health ( Z014 ), the Research Excellence Scholarships of Shenzhen University ( ZYZD2305 ), and the Science and Technology Innovation Projects of the State General Administration of Sports ( 23KJCX057 ).

PY - 2025

Y1 - 2025

N2 - Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) – a protease released by skeletal muscle during PA – acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.g., hippocampus and prefrontal cortex) that support performance in specific cognitive domains including memory, learning, and executive function. However, the evidence regarding the role of PA-induced changes in CTSB as a mediator of PA-induced cognitive health in humans is mixed. To guide future research, this article identifies key factors that may explain the observed heterogeneity in the findings from human studies and proposes a PA–CTSB–cognition model.

AB - Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) – a protease released by skeletal muscle during PA – acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.g., hippocampus and prefrontal cortex) that support performance in specific cognitive domains including memory, learning, and executive function. However, the evidence regarding the role of PA-induced changes in CTSB as a mediator of PA-induced cognitive health in humans is mixed. To guide future research, this article identifies key factors that may explain the observed heterogeneity in the findings from human studies and proposes a PA–CTSB–cognition model.

KW - brain health

KW - cognition

KW - CTSB

KW - exercise

KW - myokine

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UR - http://www.scopus.com/inward/citedby.url?scp=85215835381&partnerID=8YFLogxK

U2 - 10.1016/j.molmed.2024.12.010

DO - 10.1016/j.molmed.2024.12.010

M3 - Review article

C2 - 39848868

AN - SCOPUS:85215835381

SN - 1471-4914

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

ER -

Physical activity, cathepsin B, and cognitive health

Abstract

Keywords

ASJC Scopus subject areas

Online availability

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