AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Autologous Transplantation for Parkinson's Disease Patients:Feasibility and Challenge

Parkinson’s Disease(PD),second only to Alzheimer’s disease,is a neurodegenerative disease,most commonly occurring in people over the age of 65 years and is mostly caused by loss of dopamine neurons[1].Clinically,motor symptoms such as resting tremor,motor retardation,muscular rigidity,and disturbance of postural balance are the main symptoms,followed by non-motor symptoms such as cognitive impairment,autonomic nervous system dysfunction,depression,and sleep disorder[2].In 2016,>6.1 million people were affected with PD globally,2.4 times the number in 1990.The large number of affected people,coupled with the high mortality and disability rates,has placed a great burden on society[3].Traditional treatment methods mainly include drugs and surgery and are supplemented by physical therapy.