#alpha synuclein

New insights into a Parkinson’s disease protein

Benevolence Beneath

A protein that causes cells to die in Parkinson’s and other brain diseases may have a benevolent side that could be harnessed to develop new treatments. Called alpha-synuclein, the protein damages cells when many copies of it clump together to form Lewy bodies, shown here in blue within a mouse’s brain. Before it’s drawn into these clumps, alpha-synuclein typically sits inside the cell’s centre, or nucleus, alongside the DNA. Copies of this DNA are made for use elsewhere in the cell, but sometimes the copying process goes wrong and causes the genetic strands to break. New research in mice shows that alpha-synuclein rapidly moves to the site of damage, where it's thought to bind and repair the strands. It's only when the protein is trapped in cellular clumps that the damage continues unchecked – perhaps leading to disease. New treatments could protect cells by replacing or mimicking the protein.

Written by Deborah Oakley

Image from work by Allison J. Schaser and Valerie R. Osterberg, and colleagues

Department of Neurology & Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, OR, USA

Image copyright held by the original authors

Research published in Scientific Reports, July 2019

Parkinson’s Associated Protein Linked to Human Upper GI Tract Infections

Acute and chronic infections in a person’s upper gastrointestinal tract appear to be linked to Parkinson’s disease, say scientists at Georgetown University Medical Center and their collaborators at the National Institutes of Health and other institutions.

Parkinson's Protein Travels From Brain to Gut

A new laboratory study provides clues on a particular pathway of 'alpha-synuclein' diffusion.

Phosphorylated alpha-synuclein deposition is present in some postural tachycardia patients with neuropathic features. Individuals with a postural tachycardia and cutaneous phosphorylated alpha-synuclein deposition may be distinguished from other patients with neuropathic POTS.

Arguably, the subgroup of POTS in which the pathophysiology is best delineated is neuropathic POTS. In this subgroup, it is hypothesized that the postural tachycardia represents a restricted autonomic neuropathy, predominantly affecting the distal sympathetic innervation to the dependent vasculature, sparing the more proximal sympathetic cardiac innervation, thereby maintaining cardiac output and blood pressure by cardiac compensation. When this compensation fails, orthostatic hypotension ensues. From this perspective, neuropathic POTS can be positioned on the orthostatic intolerance continuum that ranges from postural tachycardia to delayed orthostatic hypotension to classical orthostatic hypotension.

Misfolded alpha-synuclein is the pathological hallmark of a group of disorders collectively known as the alpha-synucleinopathies. Autonomic dysfunction is the cardinal feature of these disorders that include pure autonomic failure, Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. A growing body of work from several laboratories has demonstrated the diagnostic utility of identifying cutaneous alpha-synuclein in these disorders...

There were statistically more men in the P-syn-positive group compared to the P-syn-negative group.

P-SYN-positive patients reported sleep-related symptoms and symptoms suggestive of gastroparesis more frequently then P-syn-negative patients. Patients without P-syn were more likely to report cognitive impairment or confusion.

The individuals with P-syn on skin biopsy reported more symptoms of REM sleep behavioral disorder and gastroparesis. In contrast, individuals without P-syn reported more symptoms of sleepiness and mental fatigue.

We report a case series of individuals with a diagnosis of POTS who have evidence of phosphorylated alpha-synuclein deposition on punch skin biopsies. Of 296 patients referred for the evaluation of POTS over a 12-month period, 22 patients had features consistent with neuropathic POTS and had skin biopsies as part of their work up. Seven of 22 patients had cutaneous alpha-synuclein deposition detected on skin biopsy.

Several lines of evidence support the concept that neuropathic POTS in some individuals is due to a restricted peripheral neuropathy; specifically, sympathetic denervation predominantly in the lower hemibody with preservation or relative preservation of cardiac sympathetic innervation. The evidence includes reports of venous denervation, impaired distal sudomotor function, lower norepinephrine spillover in the legs than the arms, quantitative sensory test results, and the association with denervation on skin biopsy. Estimates suggest that in tertiary referral center studies, a neuropathic etiology may underlie POTS in 33 to 50% of individuals. These data have prompted a search for a specific neurological cause in POTS patients and possible etiologies that have been uncovered include diabetes, Sjogren’s syndrome, and autoimmune autonomic ganglionopathy. The results of the present study should be viewed in this context, specifically, that alpha-synuclein deposition may underlie the postural tachycardia and accompanying symptoms in a subset of patients.

...in individuals with neuropathic POTS, in the face of attenuated systemic vascular resistance due to distal sympathetic denervation, blood pressure is maintained by a compensatory tachycardia that increases cardiac output. Whereas in patients with classical neurogenic orthostatic hypotension, the homeostatic reflexes that maintain blood pressure fail due to central and/or peripheral neurodegeneration.

Upper gastrointestinal symptoms, suggestive of gastroparesis, were prominent in the P-SYN-positive group who had a significantly higher total score on the validated Gastroparesis Cardinal Symptom Index compared to the POTS group without P-SYN. Gastrointestinal symptoms are common in the synucleinopathies and many studies have documented synuclein deposition throughout the gastrointestinal tract. However, symptoms in the earliest disease stage—and most studies refer to Parkinson’s disease—are usually referable to the lower gastrointestinal tract. Indeed, constipation is a prominent premotor symptom in epidemiologic studies of Parkinson’s disease and may antedate motor symptoms by >20 years. In contrast, gastroparesis is characteristically a late manifestation in Parkinson’s disease, although, paradoxically, in pathological studies, the distribution of alpha-synuclein deposition is highest in the proximal gastrointestinal tract and lowest in the rectum and colon. The relationship between this observation and the symptoms in the P-SYN patients will require further study. In contrast, in studies of POTS patients, upper gastrointestinal symptoms consistent with gastroparesis are highly prevalent, particularly in patients with neuropathic POTS.

Global Alpha Synuclein Market Ongoing Development Trend’s 2018

MarketResearchNest.com presents “Global Alpha Synuclein Market Research Report 2018” new Research to its studies database. The records spread across 117 with more than one tables and figures in it.   This comprehensive Alpha Synuclein Market research report includes a brief on these trends that can help the businesses operating in the industry to understand the market and strategize for their…