scholarly journals Minocycline inhibition of microglial rescues nigrostriatal dopaminergic neurodegeneration caused by mutant alpha-synuclein overexpression

Aging ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 14232-14243 ◽  
Author(s):  
Yong Wang ◽  
Qian Wang ◽  
Ruobing Yu ◽  
Qi Zhang ◽  
Zhonghai Zhang ◽  
...  
Keyword(s):  
Alpha Synuclein ◽  
Dopaminergic Neurodegeneration ◽  
Nigrostriatal Dopaminergic Neurodegeneration

scholarly journals Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease

2019 ◽  
Vol 9 (4) ◽  
pp. 73 ◽  
Author(s):  
Anthony Gaeta ◽  
Kim Caldwell ◽  
Guy Caldwell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alpha Synuclein ◽  
Dopamine Neurons ◽  
Genetic Modifiers ◽  
Transgenic Expression ◽  
C Elegans ◽  
Dopaminergic Neurodegeneration ◽  
Cellular Phenotypes ◽  
Functional Mechanisms

Parkinson’s Disease (PD) is the second-most common neurodegenerative disease in the world, yet the fundamental and underlying causes of the disease are largely unknown, and treatments remain sparse and impotent. Several biological systems have been employed to model the disease but the nematode roundworm Caenorhabditis elegans (C. elegans) shows unique promise among these to disinter the elusive factors that may prevent, halt, and/or reverse PD phenotypes. Some of the most salient of these C. elegans models of PD are those that position the misfolding-prone protein alpha-synuclein (α-syn), a hallmark pathological component of PD, as the primary target for scientific interrogation. By transgenic expression of human α-syn in different tissues, including dopamine neurons and muscle cells, the primary cellular phenotypes of PD in humans have been recapitulated in these C. elegans models and have already uncovered multifarious genetic factors and chemical compounds that attenuate dopaminergic neurodegeneration. This review describes the paramount discoveries obtained through the application of different α-syn models of PD in C. elegans and highlights their established utility and respective promise to successfully uncover new conserved genetic modifiers, functional mechanisms, therapeutic targets and molecular leads for PD with the potential to translate to humans.

scholarly journals Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein. Implication for dopaminergic neurodegeneration

FEBS Journal ◽  
2005 ◽  
Vol 272 (14) ◽  
pp. 3661-3672 ◽  
Author(s):  
Hong-Tao Li ◽  
Dong-Hai Lin ◽  
Xiao-Ying Luo ◽  
Feng Zhang ◽  
Li-Na Ji ◽  
...  
Keyword(s):  
Alpha Synuclein ◽  
Amino Groups ◽  
Dopaminergic Neurodegeneration

scholarly journals Nigral overexpression of alpha-synuclein in the absence of parkin enhances alpha-synuclein phosphorylation but does not modulate dopaminergic neurodegeneration

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Anne-Sophie Van Rompuy ◽  
Marusela Oliveras-Salvá ◽  
Anke Van der Perren ◽  
Olga Corti ◽  
Chris Van den Haute ◽  
...  
Keyword(s):  
Alpha Synuclein ◽  
Dopaminergic Neurodegeneration

scholarly journals Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor dysfunction and cortical atrophy, independent of protein aggregation.

2021 ◽  
Author(s):  
Haley M. Geertsma ◽  
Terry R Suk ◽  
Konrad M Ricke ◽  
Kyra Horsthuis ◽  
Jean-Louis A Parmasad ◽  
...  
Keyword(s):  
Alpha Synuclein ◽  
Motor Dysfunction ◽  
Cortical Atrophy ◽  
Nuclear Accumulation ◽  
Motor Deficits ◽  
Protein Overexpression ◽  
Dopaminergic Neurodegeneration ◽  
Disease Phenotypes ◽  
Experimental Systems ◽  
Biochemical Level

Background A growing body of evidence suggests that nuclear alpha-synuclein (aSyn) plays a role in the pathogenesis of Parkinson's disease (PD). However, this question has been difficult to address as controlling the localization of aSyn in experimental systems often requires protein overexpression, which results in aggregation. Methods We engineered SncaNLS mice which localize endogenous aSyn to the nucleus. We characterized these mice on a behavioral, histological, and biochemical level to determine whether the increase of nuclear aSyn is sufficient to elicit disease phenotypes. Results SncaNLS mice exhibit age-dependent motor deficits and altered gastrointestinal function. We found that these phenotypes were not linked to aSyn aggregation or phosphorylation. Through histological analyses, we observed motor cortex atrophy in the absence of midbrain dopaminergic neurodegeneration. We sampled cortical proteomes of SncaNLS mice and controls to determine the molecular underpinnings of these pathologies. Interestingly, we found several dysregulated proteins involved in dopaminergic signaling, namely Darpp-32, which we further confirmed was decreased in cortical samples of the SncaNLS mice compared to controls via immunoblotting. Conclusions These results suggest that chronic endogenous nuclear aSyn can elicit toxic phenotypes in mice, independent of its aggregation. This model raises key questions related to the mechanism of aSyn toxicity in PD and provides a new model to study an underappreciated aspect of PD pathogenesis.

Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions

2015 ◽  
Vol 53 (5) ◽  
pp. 2761-2777 ◽  
Author(s):  
Vinod Kumar ◽  
Brajesh Kumar Singh ◽  
Amit Kumar Chauhan ◽  
Deepali Singh ◽  
Devendra Kumar Patel ◽  
...  
Keyword(s):  
Dopaminergic Neurodegeneration ◽  
Nigrostriatal Dopaminergic Neurodegeneration ◽  
Molecular Interventions
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