Elsevier

Life Sciences

Volume 245, 15 March 2020, 117345
Life Sciences

Review article
The benefits and mechanisms of exercise training for Parkinson's disease

https://doi.org/10.1016/j.lfs.2020.117345Get rights and content

Abstract

Parkinson's disease (PD) is a significantly progressive neurodegenerative disease characterised by both motor and nonmotor disorders. The main pathological characteristics of PD consist of the loss of dopaminergic neurons and the formation of alpha-synuclein-containing Lewy bodies in the substantia nigra. Currently, the main therapeutic method for PD is anti-Parkinson medications, including levodopa, madopar, sirelin, and so on. However, the effect of pharmacological treatment has its own limitations, the most significant of which is that the therapeutic effect of dopaminergic treatments gradually diminishes with time. Exercise training, as an adjunctive treatment and complementary therapy, can improve the plasticity of cortical striatum and increase the release of dopamine. Exercise training has been proven to effectively improve motor disorders (including balance, gait, risk of falls and physical function) and nonmotor disorders (such as sleep impairments, cognitive function and quality of life) in PD patients. In recent years, various types of exercise training have been used to treat PD. In this review, we summarise the exercise therapy mechanisms and the protective effects of different types of exercise training on PD patients.

Introduction

Parkinson's disease (PD), a progressive neurodegenerative disorder, is mainly associated with many factors [1]. First, the strongest genetic risk factor of PD is a mutation in the gene encoding β-glucocerebrosidase [2]. According to previous studies, mutations of the LRRK2 gene have been found in familial and sporadic PD, and mutations of the SNCA gene (the alpha-synuclein gene) are regarded as risk factors for PD [3,4]. Furthermore, the influence of environmental factors on genetically susceptible persons plays a crucial role in the process of PD development [5]. For instance, xenobiotic exposure, such as transitional metal deposits going into vulnerable central nervous system areas, seems to interact with the genes which are regarded as risk factors for PD [5]. In addition, central nervous system infection and craniocerebral trauma, as well as exposure to pesticides and fungicides, such as rotenone and paraquat, seem to be associated with the pathological process of PD [[6], [7], [8]].

PD mainly occurs in adults who are 60 years or older, and its occurrence in men is higher than in women [9,10]. As the second most common neurodegenerative disorder, PD impacts at least 6 million people worldwide [11]. PD patients have motor and nonmotor disorders that prevent them from participating in exercise activities [12]. Motor disorders have received more attention from researchers and clinicians [13] and major motor symptoms include tremor, bradykinesia (hypokinesia or akinesia), plastic-type muscular rigidity and postural instability [14]. PD patients also have other kinds of typical motor disorders, including frozen gait, altered gait patterns and motor coordination dysfunctions [15]. Besides motor symptoms, nonmotor symptoms also influence quality of life and can include cognitive dysfunction, sleep disorder, anxiety, depression and fatigue [16]. There is an increasing amount of evidence indicating that nonmotor disorders can significantly affect quality of life, lead to disability, and cause more health-associated problems compared with a motor disorder [17]. There are also other types of symptoms that seriously affect the quality of life in PD patients, including loss of energy, negative emotions, and loss of control over one's own health [18,19]. Above all, the dysfunction caused by PD makes patients lose the ability to perform daily life activities and hence lose their independence [20].

Clinically, there are two types of treatments for PD: surgical therapy (deep brain stimulation) and medication (levodopa, dopamine agonists) [21]. l-dopa, the gold standard medication for PD motor symptoms, is a precursor of dopamine that can easily pass through the blood–brain barrier [14]. Other medications are also available, which are commonly related to L-dopa, and are classified in line with the mechanism of action so as to increase dopamine generation; these medications include catechol-o-methyl transferase (COMT) inhibitors, monoamine oxidase-B (MAO-B), and dopaminergic agonists for instance pramipexole (amantadine) [22]. Pharmacological therapy can improve PD patients' motor symptoms, but over time, the effect of dopaminergic treatments gradually diminishes, and several characteristics of motor control are resistant to pharmacological therapy [23]. Additionally, the existing medication treatments can only relieve symptoms and hence are unable to stop disease progression [24]. In recent years, two novel treatments for PD patients have emerged, including neurotrophic factor treatment and cell transplantation, but these two strategies mainly depend on highly invasive stereotaxic surgery that is accompanied by safety problems and side effects [25]. Under these circumstances, exercise, as a complementary and nonpharmacological therapy, is gaining more and more attention for the treatment of PD [26].

In 1992, Sasco et al. first reported a link between exercise and PD, and they found that exercise intervention in adulthood significantly reduced the risk of developing PD for the rest of one's lifetime [27]. Subsequently, several large-scale epidemiological research studies confirmed this beneficial role of exercise for PD [28,29]. Furthermore, Lau et al. indicated that exercise can potentially decrease the risk of worsening neurological deficits in PD [30]. As a complementary and alternative treatment, exercise can both improve the motor and nonmotor symptoms of PD patients [31]. In clinical studies, various types of exercise training, such as aerobic exercise, gait training, balance training, progressive resistance training and complementary exercise, have been used. In this review, we summarise the roles of different types of exercise training for PD patients and the related mechanisms in providing PD patients with an optimised exercise therapy and how this can delay disease progression and improve quality of life, thus benefiting the increasing number of PD patients.

Section snippets

Dysfunctions of PD

PD patients have both motor and nonmotor dysfunctions that prevent them from performing normal daily activities, and four of these dysfunctions are most common, including postural instability, gait disorder, freezing of gait, and cognitive impairments.

The involved mechanisms of exercise training in animal experiments

In recent years, researchers have conducted a series of studies to investigate the mechanisms of exercise training for PD. According to animal research, aerobic exercise exerts neurorestorative and neuroprotective effects, possibly through regulating neurotrophic factors to support synapse formation and angiogenesis, inhibiting oxidative stress and improving mitochondrial function [75]. For instance, exercise on a treadmill can increase the level of brain-derived neurotrophic factor (BDNF) and

Conclusion

Overall, various types of exercise therapy have been reported as having therapeutic effects on motor disorders and nonmotor disorders in patients with PD. Among the different kinds of exercise interventions, aerobic exercise is the most widely studied treatment and has positive effects on motor, quality of life, cognition and emotion. In addition, some new types of techniques have been used in the treatment of PD. For instance, VR technology provides patients with visual, auditory and

Declaration of competing interest

The authors declare no conflicts of interest.

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