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Abnormal Organelles and Protein Expression in Acute and Chronic Neurodegeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 July 2024 | Viewed by 1147

Special Issue Editor

Special Issue Information

Dear Colleagues,

In defining neurodegenerative disorders, we now include both slow chronic events which occur typically in Parkinson’s disease and degenerative dementia, as well as sudden acute neuronal loss, which recapitulates within a condensed time interval with most molecular events taking place in classic degenerative disorders, as demonstrated within ischemic penumbra following an ischemic stroke or prolonged epileptic discharges within epileptic penumbra. In keeping with such a wide definition of neurodegeneration, we should also include abnormal events which take place within neurons during reiterated exposure to drugs of abuse, which characterize neurodegeneration in the addicted brain. Similarly, psychiatric disorders such as bipolar disorders may feature degenerative phenomena.

In all conditions, a specific alteration to key organelles can often be described, and altered protein expression and protein clearance occur per se or related to the dysfunctional clearance organelles such as the autophagosomes, lysosomes, etc. The aim of this Special Issue is to gather evidence from various research field which share similar steps in producing a loss of neuronal integrity within specific brain areas ex vivo and in vivo, cell lines in vitro or protein conformation within in tubo systems. As such, the Special Issue focuses on collecting various findings from different research fields to represent a comprehensive overview of the pathways and subcellular components which characterize a variety of degenerative phenomena. Such a multi-faceted approach should attract scientists from different fields of neuroscience with expertise in various methods and topics.

Prof. Dr. Francesco Fornai
Guest Editor

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Keywords

  • brain ischemia
  • epileptic damage
  • basal ganglia pathology
  • catecholamine cell damage
  • excitotoxicity
  • autophagy
  • dopamine system norepinephrine system
  • protein unfolding
  • protein misfolding
  • cholinergic system

Published Papers (1 paper)

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Research

19 pages, 4415 KiB  
Article
SARS-CoV-2 Nucleocapsid Protein Induces Tau Pathological Changes That Can Be Counteracted by SUMO2
by Franca Orsini, Marco Bosica, Annacarla Martucci, Massimiliano De Paola, Davide Comolli, Rosaria Pascente, Gianluigi Forloni, Paul E. Fraser, Ottavio Arancio and Luana Fioriti
Int. J. Mol. Sci. 2024, 25(13), 7169; https://doi.org/10.3390/ijms25137169 - 28 Jun 2024
Viewed by 940
Abstract
Neurologic manifestations are an immediate consequence of SARS-CoV-2 infection, the etiologic agent of COVID-19, which, however, may also trigger long-term neurological effects. Notably, COVID-19 patients with neurological symptoms show elevated levels of biomarkers associated with brain injury, including Tau proteins linked to Alzheimer’s [...] Read more.
Neurologic manifestations are an immediate consequence of SARS-CoV-2 infection, the etiologic agent of COVID-19, which, however, may also trigger long-term neurological effects. Notably, COVID-19 patients with neurological symptoms show elevated levels of biomarkers associated with brain injury, including Tau proteins linked to Alzheimer’s pathology. Studies in brain organoids revealed that SARS-CoV-2 alters the phosphorylation and distribution of Tau in infected neurons, but the mechanisms are currently unknown. We hypothesize that these pathological changes are due to the recruitment of Tau into stress granules (SGs) operated by the nucleocapsid protein (NCAP) of SARS-CoV-2. To test this hypothesis, we investigated whether NCAP interacts with Tau and localizes to SGs in hippocampal neurons in vitro and in vivo. Mechanistically, we tested whether SUMOylation, a posttranslational modification of NCAP and Tau, modulates their distribution in SGs and their pathological interaction. We found that NCAP and Tau colocalize and physically interact. We also found that NCAP induces hyperphosphorylation of Tau and causes cognitive impairment in mice infected with NCAP in their hippocampus. Finally, we found that SUMOylation modulates NCAP SG formation in vitro and cognitive performance in infected mice. Our data demonstrate that NCAP induces Tau pathological changes both in vitro and in vivo. Moreover, we demonstrate that SUMO2 ameliorates NCAP-induced Tau pathology, highlighting the importance of the SUMOylation pathway as a target of intervention against neurotoxic insults, such as Tau oligomers and viral infection. Full article
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