https://pubmed.ncbi.nlm.nih.gov/32710729/
T-006 is a potent neuroprotective and neuroregenerative agent that may have therapeutic potential in the treatment of PD
T-006
Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways
https://www.aging-us.com/article/103551
https://www.ncbi.nlm.nih.gov/pubmed/32710729?dopt=Abstract
TITLE:
Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways.
DESCRIPTION:
Related Articles
Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways.
Aging (Albany NY). 2020 Jul 24;12:
Authors: Chen H, Cao J, Zha L, Wang P, Liu Z, Guo B, Zhang G, Sun Y, Zhang Z, Wang Y
Abstract
T-006, a new derivative of tetramethylpyrazine, has been recently found to protect against 6-hydroxydopamine (6-OHDA)-induced neuronal damage and clear α-synuclein (α-syn) by enhancing proteasome activity in an α-syn transgenic Parkinson’s disease (PD) model. The effect of T-006 on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model, however, has not been tested and T-006’s neuroprotective mechanisms have not been fully elucidated. In this study, we further investigated the neuroprotective and neurogenic effects of T-006 and explored its underlying mechanism of action in both cellular and animal PD models. T-006 was able to improve locomotor behavior, increase survival of nigra dopaminergic neurons and boost striatal dopamine levels in both MPTP- and 6-OHDA-induced animals. T-006 treatment restored the altered expressions of myocyte enhancer factor 2D (MEF2D), peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1α (PGC1α) and NF-E2-related factor 1/2 (Nrf1/2) via modulation of Akt/GSK3β signaling. T-006 stimulated MEF2, PGC1α and Nrf2 transcriptional activities, inducing Nrf2 nuclear localization. Interestingly, T-006 promoted endogenous adult neurogenesis toward a dopaminergic phenotype by activating brain-derived neurotrophic factor (BDNF) and cAMP responsive element-binding protein (CREB) in 6-OHDA rats. Our work demonstrated that T-006 is a potent neuroprotective and neuroregenerative agent that may have therapeutic potential in the treatment of PD.
PMID: 32710729 [PubMed – as supplied by publisher]
PMID:
PubMed:32710729
DATE FOUND:
07/28/20 06:01AM
LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32710729?dopt=Abstract