Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice

Life Sciences ◽  
2019 ◽  
Vol 232 ◽  
pp. 116600 ◽  
Author(s):  
Gejuan Zhang ◽  
Geqiang Yang ◽  
Jian Liu
2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Aarushi Sahni ◽  
Nicole Katchur

The Blood-Brain Barrier (BBB) is a highly selective filter responsible for allowing certain gases such as oxygen and lipid-soluble molecules to pass (Anand 2014). Its selectiveness makes it challenging for many therapeutics to combat Alzheimer’s and Parkinson’s disease with external drug therapies. Large-molecule drug therapies never pass the BBB while small-molecule drugs pass only about 5% of the time (Pardridge 2005). In Alzheimer’s disease, tight junctions between endothelial cells degrade, causing an unregulated accumulation of amyloid-β (Aβ) protein (Ramanathan 2015). Consequently, this leads to the formation of neurofibrillary tangles that cut off the nutrient supply to the brain cells and kill neurons (Ramanathan 2015). In Parkinson’s disease, astrocyte mutations cause a build-up of α-synuclein (αSyn) which affects the neuroinflammatory response and causes dysfunction in dopaminergic neurons (Booth 2017; Meade 2019). New drug therapies for Alzheimer’s and Parkinson’s continue to undergo trials; some such as FPS-ZM1 and tilavonemab for Alzheimer’s and Ravicti for Parkinson’s have shown promising results. In addition, similarities in dysfunction for both diseases and some types of cancer have sparked possibilities in retargeting cancer drugs to improve Alzheimer's and Parkinson’s pathologies. This review will summarize current therapeutic advancements for Alzheimer’s and Parkinson’s disease and their possible future contributions.


2021 ◽  
Author(s):  
Sílvia Cabré ◽  
Verónica Alamilla ◽  
Niamh Moriarty ◽  
Abhay Pandit ◽  
Eilís Dowd

In cell replacement approaches for Parkinson's disease, the intra-cerebral implantation of dopamine neuron-rich grafts generates a neuroinflammatory response to the grafted cells that contributes to its varied outcome. Thus, the aim of this study was to fabricate an anti-inflammatory cytokine-eluting collagen hydrogel capable of delivering IL-10 to the brain for reduction of the neuroinflammatory response to intra-cerebral cellular grafts. In vitro assessment revealed that crosslinker concentration affected the microstructure and gelation kinetics of the hydrogels and their IL-10 elution kinetics, but not their cytocompatibility or the functionality of the eluted IL-10. In vivo evaluation revealed that the hydrogels were capable of delivering and retaining IL-10 in the rat striatum, and reducing the neuroinflammatory (microglial) response to hydrogel-encapsulated grafts. In conclusion, IL-10-eluting collagen hydrogels may have beneficial anti-inflammatory effects in the context of cellular brain repair therapies for Parkinson's disease and should be investigated further.


Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1359 ◽  
Author(s):  
Edwards III ◽  
Gamez ◽  
Armijo ◽  
Kramm ◽  
Morales ◽  
...  

: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of motor control due to a wide loss of dopaminergic neurons along the nigro-striatal pathway. Some of the mechanisms that contribute to this cell death are inflammation, oxidative stress, and misfolded alpha-synuclein-induced toxicity. Current treatments are effective at managing the early motor symptoms of the disease, but they become ineffective over time and lead to adverse effects. Previous research using intracerebral stem cell therapy for treatment of PD has provided promising results; however, this method is very invasive and is often associated with unacceptable side effects. In this study, we used an MPTP-injected mouse model of PD and intravenously administered neural precursors (NPs) obtained from mouse embryonic and mesenchymal stem cells. Clinical signs and neuropathology were assessed. Female mice treated with NPs had improved motor function and reduction in the neuroinflammatory response. In terms of safety, there were no tumorigenic formations or any detectable adverse effect after treatment. Our results suggest that peripheral administration of stem cell-derived NPs may be a promising and safe therapy for the recovery of impaired motor function and amelioration of brain pathology in PD.


2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Alyssa Nease ◽  
Emir Malovic ◽  
Naveen Kondru ◽  
Huajun Jin ◽  
Vellareddy Anantharam ◽  
...  

Author(s):  
Yunhu Fan ◽  
M. Maghimaa ◽  
Arunachalam Chinnathambi ◽  
Sulaiman Ali Alharbi ◽  
Vishnu Priya Veeraraghavan ◽  
...  

Glia ◽  
2016 ◽  
Vol 64 (9) ◽  
pp. 1590-1604 ◽  
Author(s):  
Bevan S. Main ◽  
Moses Zhang ◽  
Kate M. Brody ◽  
Scott Ayton ◽  
Tony Frugier ◽  
...  

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