Summary: This review synthesizes evidence from 129 studies examining how exercise-induced muscle signaling protects against Parkinson’s disease (PD). It highlights the role of sarcopenia — the age-related loss of muscle mass, strength, and function — in worsening PD outcomes and explains how muscle-derived signaling molecules released during exercise can support brain health and slow disease progression.
Key Facts
- Sarcopenia as a Modifiable Risk Factor: Age-related muscle wasting and functional decline are linked to poorer prognosis in PD, including more frequent falls, faster cognitive decline, and reduced independence.
- Skeletal Muscle as an Endocrine Organ: Contracting muscle releases hormone-like signaling molecules — called exerkines — into the bloodstream that influence distant organs, including the brain.
- Key Protective Exerkines: Important muscle-derived messengers identified include brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), irisin, cathepsin B, myostatin, and growth/differentiation factor 15 (GDF15).
- Substantia Nigra Neuroprotection: Exerkines produce antioxidant and anti-inflammatory effects that support dopamine-producing neurons in the substantia nigra, improving mitochondrial function and resilience to stress.
- Clinical Prescriptive Consensus: Current guidelines recommend early, sustained, individualized, multimodal exercise programs combining resistance, aerobic, and balance training to preserve muscle and promote neuroprotection.
Source: Chinese Medical Journals Publishing House Co
Parkinson’s disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms that increase with age. As populations age globally, PD represents a growing public health challenge. Alongside classical neurodegenerative mechanisms such as dopaminergic neuron loss and α-synuclein aggregation, accumulating evidence points to skeletal muscle health as a key determinant of functional outcomes and prognosis.
Sarcopenia — the progressive decline in muscle mass, strength, and functional capacity — is common in older adults and particularly prevalent in people with PD. In PD patients, sarcopenia compounds motor deficits, increases fall risk, accelerates cognitive decline, and reduces quality of life. For these reasons, improving muscle strength and function through exercise has emerged as an important therapeutic target with benefits that extend beyond mobility.
A team led by Dr. Miguel Germán Borda reviewed 129 experimental, observational, and interventional studies to clarify how exercise and muscle-derived signaling molecules interact with brain health in PD. The review consolidates current knowledge about muscle–brain crosstalk and offers practical implications for exercise-based care.
The evidence supports multiple exercise modalities. Aerobic activities such as brisk walking, jogging, or cycling raise cardiovascular fitness and aid brain perfusion. Resistance or strength training, including weight-bearing exercises and progressive resistance programs, preserves and builds muscle mass. Balance and stability practices, such as Tai Chi and targeted balance routines, reduce fall risk. Multimodal programs that combine aerobic, resistance, and balance elements deliver the most comprehensive benefits for gait, balance, mood, cognition, and overall quality of life in people with PD.
Mechanistically, contracting muscle releases exerkines into the circulation. These molecules act in a hormone-like manner to modulate inflammation, oxidative stress, and mitochondrial function in distant tissues, including the brain. Key exerkines such as BDNF, IGF-1, irisin, and cathepsin B have been associated with enhanced synaptic plasticity, neuronal survival, and improved metabolic resilience. Others, like myostatin and GDF15, influence muscle remodeling and systemic responses to exercise. Collectively, these signals help dopaminergic neurons withstand stressors that otherwise accelerate degeneration.
Clinical guidance now emphasizes the importance of initiating exercise early and maintaining it long term. Recommendations favor individualized, progressive, multimodal programs that adapt to each patient’s changing capacity. Regular participation in strength and balance training appears particularly effective at reducing falls and disability while supporting cognitive and mood outcomes.
In summary, exercise provides dual benefits for people with Parkinson’s disease: preserving muscle function and delivering protective molecular signals from muscle to brain. Healthy muscle and sustained physical activity can slow some aspects of disease progression by releasing exerkines that support neuronal health. Further research is needed to define optimal exercise dose, frequency, and the most relevant exerkines for long-term neuroprotection.
Key Questions Answered:
A: Sarcopenia causes progressive loss of muscle mass and strength, which exacerbates PD-related motor deficits, increases postural instability and fall risk, speeds cognitive decline, and accelerates loss of independence.
A: Exerkines are signaling proteins and peptides released by skeletal muscle during contraction. They enter the bloodstream and can influence remote organs, including crossing or modulating the blood–brain barrier to affect neural function.
A: Multimodal programs that combine resistance (strength) training, aerobic conditioning, and balance/stability exercises yield the broadest benefits, preserving muscle and promoting exerkine-mediated neuroprotection.
Editorial Notes:
- Edited by an editorial team specializing in neuroscience reporting.
- Journal article reviewed in full and summarized for clinicians and the general public.
- Contextual commentary added by the editorial staff to aid understanding.
About this Parkinson’s disease research news
Author: Ningning Wang
Source: Chinese Medical Journals Publishing House Co
Contact: Ningning Wang – Chinese Medical Journals Publishing House Co
Image: Image credited to Neuroscience News
Original Research: Open access. “Exercise, exerkines, and muscle–brain crosstalk in Parkinson’s disease” by Salomón Páez-García, Edgar Alvarado, Alejandro Cuevas, Laura Valverde, Eduardo Salinas, Kevin O’Hara-Veintimilla, María Cruz Rodríguez-Oroz, Miguel Germán Borda. DOI: 10.1002/nep3.70032
Abstract
Exercise, exerkines, and muscle–brain crosstalk in Parkinson’s disease
Parkinson’s disease is driven by dopaminergic neuron loss and α-synuclein accumulation, producing both motor and non-motor symptoms. Beyond neuronal pathology, skeletal muscle health — particularly the presence or absence of sarcopenia — plays an important role in determining functional outcomes. This narrative review synthesizes evidence on how exercise, muscle status, and exerkine signaling interact to influence neuroprotection and patient-centered endpoints.
A systematic search of the literature up to October 2025 identified 129 relevant studies spanning basic science, observational cohorts, and clinical trials. These studies document the high prevalence of sarcopenia in PD, the prognostic value of simple measures like grip strength, and the consistent clinical benefits of aerobic, resistance, balance, and multimodal exercise programs for gait, balance, mood, cognition, and quality of life.
Mechanistic data support a model in which contracting skeletal muscle functions as an endocrine organ, releasing exerkines that modulate inflammation, oxidative stress, and mitochondrial function in the brain. Through these pathways, exerkines support dopaminergic neuron survival, enhance synaptic plasticity, and increase neuronal resilience to degenerative stressors. Current international guidelines therefore recommend individualized, multimodal exercise interventions initiated early and maintained long term as a promising nonpharmacological approach to mitigate neurodegeneration and functional decline in PD.