Alpha-Synuclein in Peripheral Tissues in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder. To date, the diagnosis of PD relies mainly on clinical manifestations whereas neuropathological confirmation of the brain is only possible with postmortem studies. Neuronal loss in the substantia nigra pars compacta (SNc) associated with Lewy bodies/neurites is the pathological hallmark feature of PD. The major component of Lewy pathology (LP) is misfolded alpha-synuclein (α-SYN). There is evidence that the distribution of LP is not only limited to the brain but extends to peripheral tissues, including gastrointestinal tract, salivary glands, olfactory mucosa, skin, retina, adrenal gland, and heart. Sensitivity and specificity of α-SYN detection in PD vary greatly among studies due to methodological heterogeneity, such as sampling sites and size, tissue preparation, staining techniques, and antibodies used. Of note, α-SYN has also been found in preclinical and prodromal PD. Further in vivo studies focusing on favorable biopsy sites and standard techniques are needed to get better understanding of α-SYN deposits in preclinical, prodromal, and clinical PD.

Fermented Soy Products: Beneficial Potential in Neurodegenerative Diseases

“…The pathogenesis of PD has been speculated to be associated with the GI tract as α-synuclein deposition was observed in the peripheral nervous system, especially in the enteric and pelvic plexus, of patients with PD [132]. A subsequent study suggested that the PD pathology originates from the peripheral organs in which α-synuclein is seeded, such as the GI tract and nasal cavity, before being retrograde transported to the cerebral cortex through the vagal nerve [132,133]. Furthermore, many patients with PD experience hyposmia and GI problems prior to the manifestation of classical PD symptoms, and patients with inflammatory bowel disease are also at a higher risk of developing PD [134].…”

Parkinson's disease and skin

“…Abnormal α-syn aggregates have been demonstrated in various peripheral tissues, including the skin, salivary glands, adrenal glands, heart, retina, olfactory mucosa, and gastrointestinal tract [12,13]. Peripheral α-syn pathology may precede widespread central disease and thus potentially account for prodromal symptoms of PD (dysautonomia, including hypo-or hyperhidrosis, constipation, orthostatic hypotension, urinary and erectile dysfunction, anosmia etc.)…”

“…transdermal patches, subcutaneous injection, percutaneous endoscopic gastrostomy for levodopa/carbidopa intestinal gel, and implantation of hardware in deep brain stimulation [DBS]). α-synuclein (α-syn), which plays a central role in PD pathogenesis [11], has been demonstrated over the past few decades to be present in multiple peripheral tissues, including skin [12,13]. This small protein (140 amino acids), involved in a variety of cellular mechanisms, undergoes misfolding and aggregation in the brain as well as in the skin [14], and may contribute to some non-motor symptoms [15].…”

Alpha Synuclein Connects the Gut-Brain Axis in Parkinson’s Disease Patients – A View on Clinical Aspects, Cellular Pathology and Analytical Methodology

“…The challenge is still the discrimination of patients and controls utilizing GIT-derived samples and an aSyn specific detection system. From a clinical but also cell-biological and biochemical view there are some arguments that favor GIT-specimens (especially from the colon) over other described sources as e.g., skin or blood (Fayyad et al, 2019;Ma et al, 2019). Interestingly, mice overexpressing human aSyn in neuronal cells (CNS and ENS), exhibit intestinal dysfunction besides the motor impairments (Chesselet et al, 2012).…”