The tight association between α-Syn and the molecular pathology of PD has generatly increaed the interest in using the α-Syn species as biomarkers to diagnose early PD. α-Syn is not confined to the central nervous system
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Authors: Haoran Peng, Siyuan Chen, Shaopu Wu, Xiaoxue Shi, Jianjun Ma, Hongqi Yang, Xue Li


Open AccessEditor's Choice

Journal of the Neurological Sciences.  REVIEW ARTICLE| VOLUME 451, 120730, AUGUST 15, 2023

Open Access

DOI: https://doi.org/10.1016/j.jns.2023.120730 ⧉


Highlights

  • Aberrant αlpha-Synuclein aggregations are a molecular and clinical hallmark of Parkinson's disease.
  • Skin is a promising organ for research on biomarkers for the diagnosis of Parkinson's disease.
  • The density of aggregating αlpha-Synuclein in skin biopsy local lesions is higher in patients who present with autonomic dysfunction.
  • Skin biopsy manipulation is a well-established technique that is the gold standard for diagnosis of skin-related lesions.

 


Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, is the leading neurodegenerative movement disorder worldwide. It affects 0.2% of the population globally and imposes a significant global disease burden. The prevalence of PD doubled between 1990 and 2016, up to 1% of people aged over 60 years and 4% of people aged over 80 years have PD, which reflecting an exponential growth in its prevalence with age. PD is a chronically progressive disease with a high prevalence and disability rate that imposes heavy economic and health burdens on families and society.

Alpha-synuclein (α-Syn) is the most prominent protein in Lewy bodies (LBs), aberrant α-Syn aggregations in the perinuclear area, axons, and dendrites of neurones in diverse brain regions are a pathological hallmark of PD. Moreover, the accumulation of α-Syn is the major pathological element in the brain that interferes with signal transduction, and is theorised as the main pathological factor in the clinical symptoms of PD. Currently, research on skin biopsies in PD is a promising direction, as biopsy is simple and easy to perform with a relatively high rate of accurate results. This method also provides new valuable data to help neurologists better understand the pathological mechanisms of PD.

The tight association between α-Syn and the molecular pathology of PD has generatly increaed the interest in using the α-Syn species as biomarkers to diagnose early PD. α-Syn is not confined to the central nervous system, it is also present in the peripheral tissues, such as human skin. The assessment of skin α-Syn has the potential to be a diagnostic method that not only has excellent sensitivity, specificity, and reproducibility, but also convenient and acceptable to patients.

In this review, we (i) integrate the biochemical, aggregation and structural features of α-Syn; (ii) map the distribution of the α-Syn species present in the brain, biological fluids, and peripheral tissues; and (iii) present a critical and comparative analysis of previous studies that have measured α-Syn in the skin.

Finally, we provide an outlook on the future of skin biopsy as a diagnostic approach for PD, and highlight its potential implications for clinical trials, clinical decision-making, treatment strategies as well as the development of new therapies.

 

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