期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms241612825
关键词
PKC epsilon; PRKCE; amyotrophic lateral sclerosis; neurodegeneration; Bryostatin-1
This study found a significant decrease in PKC epsilon expression in patients with amyotrophic lateral sclerosis (ALS), and the activation of PKC epsilon by Bryostatin-1 produced long-term survival in degenerating cells. These results suggest that PKC epsilon may play an important role in the pathophysiology of ALS and its pharmacological modulation could be a potential neuroprotective strategy.
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, characterized by a progressive depletion of upper and lower motor neurons (MNs) in the brain and spinal cord. The aberrant regulation of several PKC-mediated signal transduction pathways in ALS has been characterized so far, describing either impaired expression or altered activity of single PKC isozymes ( alpha,beta, zeta and delta). Here, we detailed the distribution and cellular localization of the epsilon-isozyme of protein kinase C (PKC epsilon) in human postmortem motor cortex specimens and reported a significant decrease in both PKC epsilon mRNA (PRKCE) and protein immunoreactivity in a subset of sporadic ALS patients. We furthermore investigated the steady-state levels of both pan and phosphorylated PKC epsilon in doxycycline-activated NSC-34 cell lines carrying the human wild-type (WT) or mutant G93A SOD1 and the biological long-term effect of its transient agonism by Bryostatin-1. The G93A-SOD1 cells showed a significant reduction of the phosphoPKC epsilon/panPKC epsilon ratio compared to the WT. Moreover, a brief pulse activation of PKC epsilon by Bryostatin-1 produced long-term survival in activated G93A-SOD1 degenerating cells in two different cell death paradigms (serum starvation and chemokines-induced toxicity). Altogether, the data support the implication of PKC epsilon in ALS pathophysiology and suggests its pharmacological modulation as a potential neuroprotective strategy, at least in a subgroup of sporadic ALS patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据