Physical activity, cathepsin B, and cognitive health

Qian Yu¹, Zhihao Zhang², Fabian Herold³, Sebastian Ludyga⁴, Jin Kuang⁵, Yanxia Chen⁶, Zijun Liu², Kirk I Erickson⁷, Bret H Goodpaster⁸, Boris Cheval⁹, Dominika M Pindus¹⁰, Arthur F Kramer¹¹, Charles H Hillman¹², Teresa Liu-Ambrose¹³, Keith W Kelley¹⁴, Hyo Youl Moon¹⁵, Aiguo Chen¹⁶, Liye Zou¹⁷

Affiliations

¹ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China; Faculty of Education, University of Macau, Macau, China.
² Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China.
³ Research Group on Degenerative and Chronic Diseases, Movement, Faculty of Health Sciences Brandenburg, University of Potsdam, Potsdam, 14476, Germany.
⁴ Department of Sport, Exercise and Health, University of Basel, Grosse Allee 6, CH-4052 Basel, Switzerland.
⁵ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China; Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁶ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China; Department of Physical Education, Shanghai Jiaotong University, Shanghai, China.
⁷ Department of Neuroscience, AdventHealth Research Institute, Orlando, FL, USA.
⁸ AdventHealth Translational Research Institute, AdventHealth, Orlando, FL, USA.
⁹ Department of Sport Sciences and Physical Education, Ecole Normale Supérieure Rennes, Bruz, France; Univ Rennes, École normale supérieure de Rennes, VIPS(2), F-35000 Rennes, France.
¹⁰ Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹¹ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Center for Cognitive and Brain Health, Northeastern University, Boston, MA, 02115, USA; Department of Psychology, Northeastern University, Boston, MA, 02115, USA.
¹² Center for Cognitive and Brain Health, Northeastern University, Boston, MA, 02115, USA; Department of Psychology, Northeastern University, Boston, MA, 02115, USA; Department of Physical Therapy, Movement, and Rehabilitation Sciences, Northeastern University, Boston, MA, 02115, USA.
¹³ Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada; Centre for Aging SMART (Solutions for Mobility, Activity, Rehabilitation, and Technology), Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada; Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
¹⁴ Department of Pathology, College of Medicine, and Department of Animal Sciences, College of Agricultural, Consumer, and Environmental Sciences (ACES), University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁵ Department of Physical Education, College of Education, Seoul National University, Seoul, Republic of Korea; Institute of Sport Science, Seoul National University, Seoul, Republic of Korea; Institute on Aging, Seoul National University, Seoul, Republic of Korea; Learning Sciences Research Institute, Seoul National University, Seoul, Republic of Korea.
¹⁶ Nanjing Sport Institute, Nanjing, China. Electronic address: agchen@nsi.edu.cn.
¹⁷ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China. Electronic address: liyezou123@gmail.com.

PMID: 39848868
DOI: 10.1016/j.molmed.2024.12.010

Review

Physical activity, cathepsin B, and cognitive health

Qian Yu et al. Trends Mol Med. 2025 Jul.

. 2025 Jul;31(7):595-609.

doi: 10.1016/j.molmed.2024.12.010. Epub 2025 Jan 23.

Authors

Affiliations

¹ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China; Faculty of Education, University of Macau, Macau, China.
² Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China.
³ Research Group on Degenerative and Chronic Diseases, Movement, Faculty of Health Sciences Brandenburg, University of Potsdam, Potsdam, 14476, Germany.
⁴ Department of Sport, Exercise and Health, University of Basel, Grosse Allee 6, CH-4052 Basel, Switzerland.
⁵ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China; Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁶ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China; Department of Physical Education, Shanghai Jiaotong University, Shanghai, China.
⁷ Department of Neuroscience, AdventHealth Research Institute, Orlando, FL, USA.
⁸ AdventHealth Translational Research Institute, AdventHealth, Orlando, FL, USA.
⁹ Department of Sport Sciences and Physical Education, Ecole Normale Supérieure Rennes, Bruz, France; Univ Rennes, École normale supérieure de Rennes, VIPS(2), F-35000 Rennes, France.
¹⁰ Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹¹ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Center for Cognitive and Brain Health, Northeastern University, Boston, MA, 02115, USA; Department of Psychology, Northeastern University, Boston, MA, 02115, USA.
¹² Center for Cognitive and Brain Health, Northeastern University, Boston, MA, 02115, USA; Department of Psychology, Northeastern University, Boston, MA, 02115, USA; Department of Physical Therapy, Movement, and Rehabilitation Sciences, Northeastern University, Boston, MA, 02115, USA.
¹³ Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada; Centre for Aging SMART (Solutions for Mobility, Activity, Rehabilitation, and Technology), Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada; Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
¹⁴ Department of Pathology, College of Medicine, and Department of Animal Sciences, College of Agricultural, Consumer, and Environmental Sciences (ACES), University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁵ Department of Physical Education, College of Education, Seoul National University, Seoul, Republic of Korea; Institute of Sport Science, Seoul National University, Seoul, Republic of Korea; Institute on Aging, Seoul National University, Seoul, Republic of Korea; Learning Sciences Research Institute, Seoul National University, Seoul, Republic of Korea.
¹⁶ Nanjing Sport Institute, Nanjing, China. Electronic address: agchen@nsi.edu.cn.
¹⁷ Body-Brain-Mind Laboratory, School of Psychology, Shenzhen University, Shenzhen, 518060, China. Electronic address: liyezou123@gmail.com.

PMID: 39848868
DOI: 10.1016/j.molmed.2024.12.010

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: CTSB; brain health; cognition; exercise; myokine.

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Declaration of interests The authors declare no competing interests.

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Physical activity, cathepsin B, and cognitive health

Affiliations

Physical activity, cathepsin B, and cognitive health

Authors

Affiliations

Abstract

Conflict of interest statement

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