Parkinson's Disease (PD) is currently considered a systemic neurodegenerative disease manifested with not only motor but also non-motor symptoms. In particular, weight loss and malnutrition, a set of frequently neglected non-motor symptoms, are indeed negatively associated with the life quality of PD patients. Moreover, comorbidity of weight loss and malnutrition may impact disease progression, giving rise to dyskinesia, cognitive decline and orthostatic hypotension, and even resulting in disability and mortality. Nevertheless, the underlying mechanism of weight loss and malnutrition in PD remains obscure and possibly involving multitudinous, exogenous or endogenous, factors. What is more, there still does not exist any weight loss and malnutrition appraision standards and management strategies. Given this, here in this review, we elaborate the weight loss and malnutrition study status in PD and summarize potential determinants and mechanisms as well. In conclusion, we present current knowledge and future prospects of weight loss and malnutrition in the context of PD, aiming to appeal clinicians and researchers to pay a closer attention to this phenomena and enable better management and therapeutic strategies in future clinical practice.

Recent researches regarding to exosomal involvement in alpha-synuclein (α-syn) transmission relating to the pathological process of Parkinson’s disease (PD) have attracted considerable attention. It is highly desirable to make clear the diffusion process and cellular uptake of α-syn-associated exosomes and the underlying mechanism of exosomes-involved communication in the synucleinopathy pathogenesis. To determine the contribution of α-syn-associated exosomes to the initiation and progression of PD, plasma exosomes derived from PD patients were stereotaxically injected into the striatum of mice brains. Exosomes extracted from plasma diagnosed with PD contained monomeric and oligomeric α-syn. Here, we found that microglia display a high potency for uptake of plasma exosomes derived from PD patients, and therefore could be activated by exogenous exosomes in vitro and in vivo. In addition, immunofluorescent double staining verified the transfer of exogenous human exosomal α-syn to neurons. The release of human exosomal α-syn from microglia may facilitate this propagation. Finally, we described a mechanism underlying this potential role of microglia in the transmission of exosomal α-syn. Specifically, exogenous exosomes were found to dysregulate autophagy of the BV2 mouse microglia cell line with presentation of increased accumulation of intracellular α-syn and accelerated secretion of α-syn into extracellular space. These results suggest that microglia play a crucial role in the transmission of α-syn via exosomal pathways, in additional to idea that the progression of PD may be altered by the modulation of exosome secretion and/or microglial states.

Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of “LB-like aggregates,” by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson’s pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials.

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Levodopa is considered to be the most effective symptomatic drug for Parkinson's disease (PD). As the disease progresses, however, the patients are likely to experience a reduced response to levodopa and develop motor fluctuations (i.e., end-of-dose wearing off and unpredictable “on-off”). Protein-rich diets and elevated plasma concentrations of large neutral amino acids have been proved to impair the therapeutic effect of levodopa by reducing its absorption and influx into the brain. On the other hand, the protein-restricted diets including low-protein diet (LPD), protein-redistribution diet (PRD) and PRD with use of low-protein products can all improve the efficacy of levodopa in patients with motor fluctuations. However, it should be noted that protein-restricted diets may also contribute to several side effects, including dyskinesia, weight loss, and malnutrition (e.g., protein and calcium insufficiency). Together, protein-restricted diets are an effective approach to improve motor fluctuations in PD patients, while long-term adherence to these diets requires monitoring for side effects.

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Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by enacting one's dreams during the REM sleep, with most of the dreams being violent or aggressive, so that patients often come to see the doctor complaining hurting themselves or bed partners during sleep. Prevalence of RBD, based on population, is 0.38-2.01 %, but much higher in patients with neurodegenerative diseases, especially synucleinopathies. RBD may herald the emergence of synucleinopathies by decades, such that it may be used as an effective early marker of neurodegenerative diseases. Pharmaceutical treatment of RBD includes clonazepam, melatonin, pramipexole, and some newly reported medications. In this review, we summarized the clinical and PSG features of RBD, the pathophysiology and the therapy of it, focusing on the correlation between neurodegenerative diseases and RBD, in order to emphasize the significance of RBD as an early marker of neurodegenerative diseases.