Synucleinopathies: New Mechanisms and Approaches to the Treatment

Dear Colleagues,

Synucleinopathies are a group of neurodegenerative diseases characterized by accumulation of α-synuclein in neurons and glial cells. This group includes Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). In these disorders, α‐synuclein accumulates and forms insoluble fibrils, which are ultimately transformed into intracellular inclusions. The first synuclein was discovered and characterized by Maroteaux and co-authors more than 30 years ago (Maroteaux et al., 1988 and 1991). Several subsequent years of collaborative work of biochemists, molecular biologists, geneticists, and structural biologists allowed us to establish association among α-synuclein, Lewy bodies, and human neurodegenerative diseases (Goedert et al., 2017). However, in spite of significant efforts to unveil synuclein’s function and disclose mechanisms of the pathology in which it is involved, many questions still remain unanswered, and an efficient treatment for these disorders is not yet found.

While early studies in synucleinopathies were mainly directed at revealing the role of synuclein misfolding, aggregation, and neurotoxicity in pathology, more recent investigations have been focused on the latest discoveries, pointing to an important role of autophagy, synuclein’s prion-like properties and  spreading of synucleins between various organs and tissues, differential splicing and epigenetic mechanisms of synucleinopathies. Among the mechanisms which play an important role in synucleinopathies are that of the peripheral nervous system, including the enteric nervous system, in the spreading of pathology, participation of small RNAs in the regulation of synuclein expression, differential splicing, post-translational modifications of synucleins changing their properties, and defects of cellular homeostasis. A role of two other members of the synuclein family, β- and γ-synuclein, in pathology also remains not completely understood and needs additional research.

In this Special Issue, we present these recent discoveries, including novel findings about the participation of α-synuclein in spreading the pathology, mechanisms regulating α-synuclein expression, and post-translational modifications. We also discuss new approaches to the development of synucleinopathies treatment.

This Special Issue will be interesting for physicians, graduate students, and medical students in the field of neurology and neurodegenerative diseases, as well as for researchers working in biochemistry, genetics, and molecular biology.

Prof. Andrei Surguchov
Guest Editor

References:

1. Maroteaux, L.; Campanelli, J.T.; Scheller, R.H. Synuclein: A neuron-specific protein localized to the nucleus and presynaptic terminal. J. Neurosci. 1988, 8, 2804–2815
2. Maroteaux, L.; Scheller, R.H. The rat brain synucleins:  Family of proteins transiently associated with neuronal membrane. Mol. Brain Res. 1991, 11, 335–343
3. Goedert, M.; Jakes, R.; Spillantini, M.G. Synucleinopathies: Twenty Years On. J. Parkinson Dis. 2017, 7, S51–S69, doi:10.3233/JPD--179005

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• misfolding
• aggregation
• Parkinson’s disease
• therapeutics
• amyloidosis
• neurodegenerative diseases
• post-translational modifications
• prion-like properties
• intercellular spreading