International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Special Issue Editors

Dr. Fabio Cavaliere

E-Mail Website
Guest Editor

Achucarro Basque Center for Neuroscience, Leioa, Spain
Interests: adult cell regeneration (neurogenesis and gliogenesis); neuron/astrocytes interaction; astrocyte biology; iPSc-derived neural cells, Parkinson disease; brain ischemia

Dr. Benjamin Dehay

E-Mail Website
Guest Editor

Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France
Interests: neurodegenerative diseases; neuronal cell death; protein aggregation; autophagy-lysosome pathway; animal models

Dr. Federico N. Soria

E-Mail Website
Guest Editor

Achucarro Basque Center for Neuroscience, Leioa, Spain
Interests: extracellular matrix; microglia; neurodegeneration; Parkinson’s disease; brain ischemia; live imaging; image analysis

Special Issue Information

Dear Colleagues,

The physiological role of the protein α -synuclein is debated; it is expressed constitutively in neurons and found in glia under certain pathological conditions. More recently, the function of α-synuclein in CNS has been associated with the regulation of exocytotic neurotransmitter release at the synapse. α-Synuclein fibrillary aggregation and spreading through neuroanatomically connected regions is a hallmark of a series of neuropathologies termed synucleinopathies that include Parkinson ’s disease, dementia with Lewy bodies, pure autonomic failure, and multiple system atrophy. Since the discovery of α-synuclein in Lewy bodies in 1997, a wealth of information has been generated on this protein. However, several questions remain unanswered: is α-synuclein aggregation a cause or effect of the pathological process? What determines the transition from the physiological to pathological state of α-synuclein? Is neuronal α-synuclein different from the α-synuclein found in glial cells? Is it worth using α-synuclein in animal models? In this Special Issue, we want to shed light upon the complex scenario of α-synuclein transition from physiology to pathology in synucleinopathies, with a wide view from the clinic to the basic experimental knowledge.

Dr. Fabio Cavaliere
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Neuroinflammation
Neurodegeneration
Gliosis
Synaptic function
Exocytosis endocytosis

Published Papers (2 papers)

Download All Papers

Research

Jump to: Review

22 pages, 8353 KiB

Open AccessArticle

The Association between α-Synuclein and α-Tubulin in Brain Synapses

by Alida Amadeo, Sara Pizzi, Alessandro Comincini, Debora Modena, Alessandra Maria Calogero, Laura Madaschi, Gaia Faustini, Chiara Rolando, Arianna Bellucci, Gianni Pezzoli, Samanta Mazzetti and Graziella Cappelletti

Int. J. Mol. Sci. 2021, 22(17), 9153; https://doi.org/10.3390/ijms22179153 - 25 Aug 2021

Cited by 9 | Viewed by 2830

Abstract

α-synuclein is a small protein that is mainly expressed in the synaptic terminals of nervous tissue. Although its implication in neurodegeneration is well established, the physiological role of α-synuclein remains elusive. Given its involvement in the modulation of synaptic transmission and the emerging role of microtubules at the synapse, the current study aimed at investigating whether α-synuclein becomes involved with this cytoskeletal component at the presynapse. We first analyzed the expression of α-synuclein and its colocalization with α-tubulin in murine brain. Differences were found between cortical and striatal/midbrain areas, with substantia nigra pars compacta and corpus striatum showing the lowest levels of colocalization. Using a proximity ligation assay, we revealed the direct interaction of α-synuclein with α-tubulin in murine and in human brain. Finally, the previously unexplored interaction of the two proteins in vivo at the synapse was disclosed in murine striatal presynaptic boutons through multiple approaches, from confocal spinning disk to electron microscopy. Collectively, our data strongly suggest that the association with tubulin/microtubules might actually be an important physiological function for α-synuclein in the synapse, thus suggesting its potential role in a neuropathological context. Full article

(This article belongs to the Special Issue α-Synuclein in Neurons and Glia: From Physiology to Pathology)

► Show Figures

Figure 1

Review

Jump to: Research

53 pages, 3591 KiB

Open AccessReview

Neurons and Glia Interplay in α-Synucleinopathies

by Panagiota Mavroeidi and Maria Xilouri

Int. J. Mol. Sci. 2021, 22(9), 4994; https://doi.org/10.3390/ijms22094994 - 8 May 2021

Cited by 27 | Viewed by 5903

Abstract

Accumulation of the neuronal presynaptic protein alpha-synuclein within proteinaceous inclusions represents the key histophathological hallmark of a spectrum of neurodegenerative disorders, referred to by the umbrella term a-synucleinopathies. Even though alpha-synuclein is expressed predominantly in neurons, pathological aggregates of the protein are also found in the glial cells of the brain. In Parkinson’s disease and dementia with Lewy bodies, alpha-synuclein accumulates mainly in neurons forming the Lewy bodies and Lewy neurites, whereas in multiple system atrophy, the protein aggregates mostly in the glial cytoplasmic inclusions within oligodendrocytes. In addition, astrogliosis and microgliosis are found in the synucleinopathy brains, whereas both astrocytes and microglia internalize alpha-synuclein and contribute to the spread of pathology. The mechanisms underlying the pathological accumulation of alpha-synuclein in glial cells that under physiological conditions express low to non-detectable levels of the protein are an area of intense research. Undoubtedly, the presence of aggregated alpha-synuclein can disrupt glial function in general and can contribute to neurodegeneration through numerous pathways. Herein, we summarize the current knowledge on the role of alpha-synuclein in both neurons and glia, highlighting the contribution of the neuron-glia connectome in the disease initiation and progression, which may represent potential therapeutic target for a-synucleinopathies. Full article

(This article belongs to the Special Issue α-Synuclein in Neurons and Glia: From Physiology to Pathology)

► Show Figures