Special Issue "Exploring the Mechanisms by which α-Synuclein Kills Cells in Parkinson Disease"
A special issue of Biomolecules (ISSN 2218-273X).
Deadline for manuscript submissions: closed (15 March 2015)
Prof. Dr. Stephan N. Witt
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130-3932, USA
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Fax: +1 318 675 5180
Interests: α-synuclein; Parkinson’s disease; endoplasmic reticulum stress; lipid homeostasis; neurodegeneration
α-Synuclein (α-syn) is a small protein that is highly expressed in dopaminergic neurons, where it is thought to regulate fusion of presynaptic vesicles with the presynaptic membrane. Monomeric α-syn is intrinsically unfolded in solution but α-helical when membrane-bound. At elevated concentrations, α-synuclein self-associates into soluble oligomers or deposits into insoluble β-amyloid fibers. Soluble tetrameric forms also probably exist in cells. Many researchers are convinced that the soluble oligomeric forms of α-syn kill cells. One question is: what cellular environment triggers α-syn to convert from a non-toxic protein into a toxic one? Another question is: how does α-syn kills cells?
We encourage scientists of diverse backgrounds (biophysical, cell biology, and animal models) and that use different model systems (yeast, fly, worm, rodents, human cells) to contribute original research or review articles that focus on the cellular conditions that promote α-syn to become toxic or the mechanisms by which α-syn kills cells.
Prof. Dr. Stephan N. Witt
Manuscript Submission Information
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- calcium homeostasis
- lipid homeostasis
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: The Interplay between alpha-Synuclein Clearance and Spreading
Authors: Tiago Fleming Outeiro
Affiliation: Department of NeuroDegeneration and Restorative Research, Center for Nanoscale
Microscopy and Molecular Physiology of the Brain, University Medical Center Goettingen, Waldweg
33, 37073 Goettingen, Germany; E-Mail: firstname.lastname@example.org
Abstract: Parkinson’s Disease (PD) is a complex neurodegenerative disorder classically characterized
by movement impairment. Pathologically, the most striking feature of PD is the loss of dopaminergic
neurons and the presence of intraneuronal protein inclusions primarily composed of alpha-synuclein
(asyn) that are known as Lewy Bodies and Lewy neurites in surviving neurons. Though the mechanisms
underlying the progression of PD pathology are unclear, accumulating evidence suggests a prion-like
spreading of asyn pathology. The intracellular homeostasis of asyn requires the proper degradation of
the protein by three mechanisms: chaperone-mediated autophagy, macroautophagy and ubiquitinproteasome.
Impairment of these pathways might drive the system towards an alternative clearance
mechanism that could involve its release from the cell. This increased release to the extracellular space
could be the basis for asyn propagation to different brain areas and, ultimately, for the spreading of
pathology and disease progression. Here, we review the interplay between asyn degradation pathways
and its intercellular spreading. The understanding of this interplay is indispensable for obtaining a better
knowledge of the molecular basis of PD and, consequently, for the design of novel avenues for
Type of Paper: Review
Title: Neurodegeneration by α-Synuclein in the Humanized Fly
Authors: Daewoo Lee
Affiliation: Neuroscience Program, Department of Biological Sciences, Ohio University, Athens, OH
45701, USA; E-Mail: Leed1@ohio.edu
Abstract: The fruit fly Drosophila melanogaster has proven to be very useful in exploring the
mechanisms underlying Parkinson’s disease. Indeed, several fly PD models have been developed by
engineering transgenic strains that express the human alpha-Synuclein (α-Syn) protein, showing
selective degeneration of dopaminergic (DA) neurons and also locomotion defects. In this commentary,
I review possible molecular and cellular mechanisms by which both wild type and mutant α-Syn proteins
degenerate DA neurons. The main focus is the role of disrupted dopamine homeostasis in α-Synmediated
neurodegeneration as excessive dopamine causes oxidative stress. The role of Lewy bodies
(LBs) in α-Syn toxicity is also discussed. Given the sophisticated genetic approaches available, the fly
PD model will continuously help to understand mechanisms underlying PD pathology and also to
develop its potential therapeutics.