Next Article in Journal
AcoMYB4, an Ananas comosus L. MYB Transcription Factor, Functions in Osmotic Stress through Negative Regulation of ABA Signaling
Previous Article in Journal
Erratum: Willenbacher, E., et al. Curcumin: New Insights into an Ancient Ingredient against Cancer. Int. J. Mol. Sci. 2019, 20, 1808
Open AccessReview

The Role of Alpha-Synuclein and Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

1
Department Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA
2
German Center for Neurodegenerative Diseases, 37075 Göttingen, Germany
3
Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, Germany
4
Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany
5
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5724; https://doi.org/10.3390/ijms21165724
Received: 13 July 2020 / Revised: 29 July 2020 / Accepted: 8 August 2020 / Published: 10 August 2020
Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence the development of both ASD and PD, with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes, which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration. View Full-Text
Keywords: alpha-synuclein; SNCA; PARK2; 22q11.2 deletion syndrome; autism spectrum disorders; Parkinson’s disease; neuronal development; neurodegeneration; synaptic dysfunction alpha-synuclein; SNCA; PARK2; 22q11.2 deletion syndrome; autism spectrum disorders; Parkinson’s disease; neuronal development; neurodegeneration; synaptic dysfunction
Show Figures

Graphical abstract

MDPI and ACS Style

Morato Torres, C.A.; Wassouf, Z.; Zafar, F.; Sastre, D.; Outeiro, T.F.; Schüle, B. The Role of Alpha-Synuclein and Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders. Int. J. Mol. Sci. 2020, 21, 5724.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop