ABSTRACT
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 (α, ß, ζ and δ). Here, we detailed the distribution and cellular localization of the ε-isozyme of protein kinase C (PKCε) in human postmortem motor cortex specimens and reported a significant decrease in both PKCε mRNA (PRKCE) and protein immunoreactivity in a subset of sporadic ALS patients. We furthermore investigated the steady-state levels of both pan and phosphorylated PKCε 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 phosphoPKCε/panPKCε ratio compared to the WT. Moreover, a brief pulse activation of PKCε 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 PKCε in ALS pathophysiology and suggests its pharmacological modulation as a potential neuroprotective strategy, at least in a subgroup of sporadic ALS patients.
Subject(s)
Amyotrophic Lateral Sclerosis , Motor Cortex , Neurodegenerative Diseases , Humans , Protein Kinase C-epsilon/genetics , Amyotrophic Lateral Sclerosis/genetics , Isoenzymes/genetics , Superoxide Dismutase-1/genetics , Bryostatins/pharmacology , Motor NeuronsABSTRACT
We are glad to introduce the Third Journal Club of Volume five, the third issue. This edition is focused on relevant studies published in the last years in the field of PhysioMechanics of Human Locomotion, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for the Sports Medicine and Movement Sciences seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture.
ABSTRACT
Research is required to minimize uncertainty and to be reproducible, that is, the design, implementation, evaluation, interpretation, and reporting of the presented data, must follow a good practice. An appropriate experimental design, an accurate execution of the study, a strict criticism of the obtained data while avoiding overestimation, as well as a suitable interpretation of main outcomes, represent key aspects in reporting and disseminating research to the scientific community. Furthermore, author contribution, responsibility, funding, acknowledgement, and adequately declaring any conflict of interest play important roles in science. The Journal of Functional Morphology and Kinesiology (JFMK), a member of the Committee on Publication Ethics (COPE), is committed to the highest scientific and ethical standards and encourages all authors to take into account and to comply, as much as possible, with the contents and issues reported in this technical note. This could be useful to improve the quality of the manuscripts and avoid misconduct, as well as to stimulate interest and debate, reflecting upon uses and misuses within our disciplines belonging to the medicine area (sports medicine and movement sciences) categories: anatomy, histology, orthopedics and sports medicine, rheumatology, sports sciences, physical therapy, sports therapy, and rehabilitation.
ABSTRACT
We are glad to introduce the seventeenth Journal Club. This edition is focused on several relevant studies published in the last years in the field of Overtraining and Exercise Addiction, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for the sport seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture.