Inhibition of transcription factor SP1 produces neuroprotective effects through decreasing MAO B activity in MPTP/MPP+ Parkinson's disease models

2018 ◽  
Vol 96 (10) ◽  
pp. 1663-1676 ◽  
Author(s):  
Lu Yao ◽  
Xing Dai ◽  
Yina Sun ◽  
Yong Wang ◽  
Qian Yang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Disease Models ◽  
Neuroprotective Effects ◽  
Mao B ◽  
Transcription Factor Sp1

Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease

2018 ◽  
Vol 125 (11) ◽  
pp. 1735-1749 ◽  
Author(s):  
Éva Szökő ◽  
Tamás Tábi ◽  
Peter Riederer ◽  
László Vécsei ◽  
Kálmán Magyar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effects ◽  
Mao B

scholarly journals KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease

2021 ◽  
Author(s):  
Min-Ho Nam ◽  
Jong-Hyun Park ◽  
Hyo Jung Song ◽  
Ji Won Choi ◽  
Siwon Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Therapeutic Potential ◽  
Motor Dysfunction ◽  
Monoamine Oxidase B ◽  
Nigrostriatal Pathway ◽  
Neuroprotective Effects ◽  
Mao B ◽  
6 Hydroxydopamine ◽  
Mptp Model

AbstractMonoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.

scholarly journals NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1649
Author(s):  
Juan A. Parga ◽  
Ana I. Rodriguez-Perez ◽  
Maria Garcia-Garrote ◽  
Jannette Rodriguez-Pallares ◽  
Jose L. Labandeira-Garcia
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Cellular Response ◽  
Therapeutic Potential ◽  
Special Focus ◽  
Ros Production ◽  
Neuroprotective Effects ◽  
Downstream Effects

Reactive oxygen species (ROS) are signalling molecules used to regulate cellular metabolism and homeostasis. However, excessive ROS production causes oxidative stress, one of the main mechanisms associated with the origin and progression of neurodegenerative disorders such as Parkinson’s disease. NRF2 (Nuclear Factor-Erythroid 2 Like 2) is a transcription factor that orchestrates the cellular response to oxidative stress. The regulation of NRF2 signalling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson’s disease. The NRF2 pathway has been shown to be affected in patients with this disease, and activation of NRF2 has neuroprotective effects in preclinical models, demonstrating the therapeutic potential of this pathway. In this review, we highlight recent advances regarding the regulation of NRF2, including the effect of Angiotensin II as an endogenous signalling molecule able to regulate ROS production and oxidative stress in dopaminergic neurons. The genes regulated and the downstream effects of activation, with special focus on Kruppel Like Factor 9 (KLF9) transcription factor, provide clues about the mechanisms involved in the neurodegenerative process as well as future therapeutic approaches.

Cassiae semen, a seed of Cassia obtusifolia, has neuroprotective effects in Parkinson’s disease models

2010 ◽  
Vol 48 (8-9) ◽  
pp. 2037-2044 ◽  
Author(s):  
Mi Sun Ju ◽  
Hyo Geun Kim ◽  
Jin Gyu Choi ◽  
Jong Hoon Ryu ◽  
Jinyoung Hur ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Models ◽  
Cassia Obtusifolia ◽  
Neuroprotective Effects

Neuroprotective effects of nitidine in Parkinson's disease models through inhibiting microglia activation: role of the Jak2–Stat3 pathway

RSC Advances ◽  
2016 ◽  
Vol 6 (75) ◽  
pp. 71328-71337 ◽  
Author(s):  
Bao Wang ◽  
Xing-qin Wang ◽  
Shao-song Yang ◽  
Xi Liu ◽  
Da-yun Feng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Microglial Activation ◽  
Microglia Activation ◽  
Disease Models ◽  
Neuroprotective Effects ◽  
Stat3 Pathway ◽  
Behavioural Function

In this work we found that nitidine could significantly suppress microglial activationviathe Jak2–Stat3 pathway and obviously improve behavioural function in Parkinson's disease (PD) animal models, which sheds light on PD treatment.

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