Early Parkinson’s Disease-Like Pathology in a Transgenic Mouse Model Involves a Decreased Cst3 mRNA Expression But Not Neuroinflammatory Response in the Brain

  title={Early Parkinson’s Disease-Like Pathology in a Transgenic Mouse Model Involves a Decreased Cst3 mRNA Expression But Not Neuroinflammatory Response in the Brain},
  author={Tatyana A. Korolenko and Alexandra B Shintyapina and Victor M. Belichenko and Alexander B. Pupyshev and A. A. Akopyan and Larisa A. Fedoseeva and G. S. Russkikh and V. A. Vavilin and Michael V. Tenditnik and C-L Lin and Tamara G. Amstislavskaya and Maria A Tikhonova},
  journal={Medical University},
  pages={66 - 78}
Abstract Pathological aggregation and accumulation of α-synuclein in neurons play a core role in Parkinson’s disease (PD) while its overexpression is a common PD model. Autophagy-lysosomal pathways are general intraneural mechanisms of protein clearance. Earlier a suppressed autophagy in the brain of young transgenic mice overexpressing the А53Т-mutant human α-synuclein (mut(PD)) was revealed. Previous studies have recognized that Cystatin C displays protective activity against… 

Figures and Tables from this paper

Restoration of Parkinson's Disease-Like Deficits by Activating Autophagy through mTOR-Dependent and mTOR-Independent Mechanisms in Pharmacological and Transgenic Models of Parkinson's Disease in Mice.
We studied the possibilities of inhibition of neurodegeneration in MPTP-induced model of Parkinson's disease (PD) in C57Bl/6J mice and transgenic model of early PD stage (5-monthold
Neuroprotective Effects of Ceftriaxone Involve the Reduction of Aβ Burden and Neuroinflammatory Response in a Mouse Model of Alzheimer’s Disease
The results confirm the potential of CEF as a promising treatment against cognitive decline from the early stages of AD progression and positioned as a potent multipurpose drug as it simultaneously targets proteostasis network and neuroinflammation.


Neuroinflammation and α-Synuclein Dysfunction Potentiate Each Other, Driving Chronic Progression of Neurodegeneration in a Mouse Model of Parkinson’s Disease
A two-hit animal model involving both a genetic lesion and an environmental trigger reproduced key features of PD and demonstrated synergistic effects of genetic predisposition and environmental exposures in the development of PD.
Cystatin C as a potential therapeutic mediator against Parkinson’s disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units
CYS C displays dual neuronal–vascular functions, promoting PC12 cell survival and angiogenesis via regulating the level of secreted VEGF in NVUs, and provides evidence that may aid in the development of an alternative approach for the treatment of PD through modulation of CYS C-mediated neuronal-vascular pathways.
NCX1 and NCX3 as potential factors contributing to neurodegeneration and neuroinflammation in the A53T transgenic mouse model of Parkinson’s Disease
In vivo and in vitro findings suggest that the reduction in NCX3 expression and activity in A53T neurons from midbrain may cause mitochondrial dysfunction and neuronal death in this brain area, whereas NCX1 overexpression in microglial cells may promote their proliferation in the striatum.
The regulatory role of cystatin C in autophagy and neurodegeneration
Using a transgenic mouse model of Parkinson’s disease (5 months old), a significant increase in osmotic susceptibility of brain lysosomes, depending on autophagy is demonstrated, an indication of an important function of this cysteine protease inhibitor in the brain.
Linking Neuroinflammation and Neurodegeneration in Parkinson's Disease
This review addresses the current concept of neuroinflammation and its involvement in PD-associated neurodegeneration and suggests that immune alterations in response to extracellular α-synuclein may play a critical role in modulating Parkinson's disease progression.
Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease
Microglial PHOX and Mac‐1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha‐synuclein
It is demonstrated that microglia are also critical in enhanced neurotoxicity induced by mutant α‐synuclein, thereby contributing to the accelerated neurodegeneration observed in fPD.
Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties
Novel targets for CEF action that might be involved into neuroprotective mechanisms at early, pre-plaque stages of AD-like pathology development are disclosed.