Abstract
Parkinson’s disease (PD) is a common and progressive neurodegenerative disease, caused by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain, which is clinically characterized by a constellation of motor and non-motor manifestations. The latter include hyposmia, constipation, depression, pain and, in later stages, cognitive decline and dysautonomia. The main pathological features of PD are neuronal loss and consequent accumulation of Lewy bodies (LB) in the surviving neurons. Alpha-synuclein (α-syn) is the main component of LB, and α-syn aggregation and accumulation perpetuate neuronal degeneration. Mutations in the α-syn gene (SNCA) were the first genetic cause of PD to be identified. Generally, patients carrying SNCA mutations present early-onset parkinsonism with severe and early non-motor symptoms, including cognitive decline. Several SNCA polymorphisms were also identified, and some of them showed association with non-motor manifestations. The functional role of these polymorphisms is only partially understood. In this review we explore the contribution of SNCA and its product, α-syn, in predisposing to the non-motor manifestations of PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its prevalence tends to increase in an age-dependent manner [1]
In a population of about 100 PD patients and 100 healthy controls from Brazil who were tested with MMSE and Frontal Assessment Battery (FAB) and genotyped for SNCA rs356219 and rs2736990, it was found that variations of both SNPs were associated with the risk of dementia
PD patients may present a peripheral neuropathy, with both an acute/subacute and chronic onset [89]. It is still controversial whether PD may itself represent a risk factor or neuropathies may be correlated with the pharmacological treatment; patients treated with continuous LD intestinal infusion have a higher incidence probably because of vitamin malabsorption with consequent accumulation of metabolites that may damage peripheral nerves [90]
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its prevalence tends to increase in an age-dependent manner [1]. Patients complain of several non-motor symptoms (NMS) that may even precede for years the onset of the motor phenotype [7]. NMS have an even greater impact on patients’ disability and caregivers’ distress compared to the motor counterpart [8] For such reasons, the spectrum of NMS has recently gained immense attention, and the last generation of clinical trials have incorporated NMS as important endpoints [9]. Α-syn can be released in the synaptic space in part through the exosomes This extracellular component plays an important role in neuronal homeostasis and may be involved in cell death [16]. Patients carrying SNCA mutations present early onset PD with severe and early non-motor symptoms, including cognitive decline [26]. We discuss the contribution of SNCA and its product, α-syn, in the non-motor manifestations of PD
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