Summary: Researchers synthesized evidence from 129 studies detailing how exercise-induced muscle signaling protects against Parkinson’s disease (PD) pathology. The authors examine the biological impact of sarcopenia, the progressive loss of muscle mass, strength, and function, in PD patients, linking muscle degradation to accelerated cognitive decline, increased fall risk, and reduced quality of life.
Key Facts
- Sarcopenia as a Modifiable Risk Factor: Age-related muscle loss and functional decline are strongly correlated with worse prognosis, higher fall frequency, accelerated cognitive impairment, and decreased independence in Parkinson’s disease.
- Skeletal Muscle as an Endocrine Organ: During physical contraction, skeletal muscle secretes signaling molecules called “exerkines” into the bloodstream, acting similarly to classical hormones to regulate central nervous system health.
- Key Protective Exerkines: Prominent muscle-derived messengers identified in the review 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 exert targeted antioxidant and anti-inflammatory effects on dopamine-producing neurons in the substantia nigra, improving their mitochondrial energy production and stress resilience.
- Clinical Prescriptive Consensus: Current guidelines advocate for early, sustained, multimodal exercise regimens, combining resistance, aerobic, and balance exercises—tailored dynamically to individual patient capacity over time.
Source: Chinese Medical Journals Publishing House Co
Parkinson’s disease (PD), a progressive neurodegenerative disorder with motor and non-motor symptoms, represents a growing global public health challenge given the rising proportion of older adults worldwide.
Recent studies have identified sarcopenia—the natural, age-related, progressive loss of muscle mass, strength, and function—as a contributor to frailty and disability. In patients with PD specifically, sarcopenia may also be associated with worse prognosis, increased falls, greater cognitive impairment, and reduced quality of life.
Consequently, research has increasingly focused on how improving muscle strength through regular exercise can improve health and functioning in older adults, with demonstrated benefits across conditions such as cancer, dementia, and PD. Understanding how exercise‐induced molecular changes contribute to neuronal health could open new therapeutic avenues to improve prognosis and quality of life in PD.
Against this backdrop, a group of researchers led by Dr. Miguel Germán Borda compiled evidence from 129 studies in a comprehensive narrative review shedding light on the muscle–brain crosstalk and how exercise could benefit PD patients.
Their findings were made available online on February 25, 2026 and were published in the journal Neuroprotection on June 01, 2026.
“Muscle is a biologically active tissue that has the potential to influence neural function. Building on this, we collected experimental, observational, and interventional data that evaluated the interplay between muscle status and exercise in PD,” says Dr. Salomón Páez-García, the first author.
The review found benefits from several exercise types. Aerobic exercises that raise the heart rate, like walking and jogging; resistance exercise or strength training, like weight lifting and squats; balance training exercises that improve stability, like standing on one leg or Tai Chi; and multimodal exercise combining several of these exercise types were found to be helpful. Regular exercise, with more strength and balance training, improved walking, balance, mood, muscle strength, thinking ability, and the overall quality of life of PD patients. Falls and disabilities decreased.
“Muscles do much more than move our body. They can act like an endocrine organ, producing hormone-like chemical messengers called ‘exerkines,’ which are released during exercise—just like the pancreas produces insulin or the thyroid gland produces thyroid hormones,” explains Dr. Borda.
When muscles contract during exercise, exerkines are released. Just like other hormones, they travel through the bloodstream and influence organs such as the brain, liver, heart, and immune system. A few important exerkines are brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), irisin, cathepsin B, myostatin, and growth/differentiation factor 15 (GDF15).
“So, the next question became, how do exerkines protect the brain?” says Dr. Páez-García. “We found that the exerkines act as a medium for the crosstalk between the muscle and the brain. Though the brain controls muscles, exercising muscles send beneficial signals back to the brain through exerkines,” he further explains.
The exerkines showed anti-inflammatory and antioxidant effects on neurons and improved their mitochondrial function. This helped the dopamine-producing nerves of the substantia nigra survive longer, resist damage, and recover from stress, making them less vulnerable to disease processes. In addition, they also improved the brain’s ability to change, adapt, and form new connections.
Current guidelines also strongly support exercise as a key part of Parkinson’s care. They recommend starting exercise early and sticking to it for as long as possible. These exercises should be a mix of aerobic, strength, and balance training, tailored to the capacity of the patient from time to time.
In summary, exercise is not just good for the muscles; it also protects the brain in people with PD. Healthy muscles and regular physical activity can slow some aspects of PD by releasing beneficial “exerkines” that communicate with the brain. More studies are needed to determine exactly how much exercise, which types, and which exerkines provide the greatest long-term neuroprotective benefits.
Key Questions Answered:
A: Sarcopenia involves the progressive loss of muscle mass, strength, and physical function. In Parkinson’s patients, sarcopenia exacerbates existing motor deficits, leading to greater postural instability, increased fall frequency, accelerated cognitive decline, and faster loss of functional independence.
A: Exerkines are hormone-like signaling molecules (such as BDNF, IGF-1, and irisin) released by skeletal muscle during physical exercise. Upon contraction, muscles secrete these factors directly into the bloodstream, allowing them to travel systemically and cross the blood-brain barrier to modulate neural function.
A: The review highlights that multimodal exercise programs combining strength training (resistance), cardiovascular conditioning (aerobic), and stability routines (balance/Tai Chi) offer the most comprehensive benefits, simultaneously preserving muscle mass and triggering robust neuroprotective exerkine release.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
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: The image is 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. Neuroprotection
DOI:10.1002/nep3.70032
Abstract
Exercise, exerkines, and muscle–brain crosstalk in Parkinson’s disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, driven by dopaminergic loss and α-synuclein accumulation. Beyond neurodegeneration, growing evidence highlights skeletal muscle health as a key determinant of prognosis, with sarcopenia and frailty contributing to greater disability, fall risk, and reduced quality of life.
This narrative review synthesizes current evidence on the interplay among exercise, muscle status, and exerkine signaling in PD, emphasizing their potential roles in neuroprotection and functional outcomes. A comprehensive literature search in PubMed and SciELO up to October 2025 identified 129 relevant studies, including experimental, observational, and interventional data.
Sarcopenia and reduced muscle strength are highly prevalent in PD and independently associated with disease severity, frailty, and falls, while grip strength has emerged as a simple biomarker of progression. Clinical trials consistently show that aerobic, resistance, and multimodal exercise programs improve gait, balance, mood, cognition, and quality of life, with progressive resistance and balance training yielding the greatest motor benefits.
At a mechanistic level, skeletal muscle functions as an active endocrine organ, releasing a variety of exercise-induced signaling molecules known as exerkines. These include brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), irisin, cathepsin B, myostatin, and growth/differentiation factor 15 (GDF15).
Together, these exerkines facilitate muscle–brain crosstalk and are thought to contribute to the neuroprotective effects of exercise in PD. Through anti-inflammatory, antioxidant, and mitochondrial regulatory pathways, they support dopaminergic neuron survival and promote synaptic plasticity and neuronal resilience.
Current international guidelines recommend individualized, multimodal programs integrating aerobic, resistance, and balance training, initiated early and maintained long-term. Exercise represents a promising, nonpharmacological intervention to mitigate neurodegeneration, sarcopenia, and functional decline in PD, although further high-quality studies are needed.
