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The ε-Isozyme of Protein Kinase C (PKCε) Is Impaired in ALS Motor Cortex and Its Pulse Activation by Bryostatin-1 Produces Long Term Survival in Degenerating SOD1-G93A Motor Neuron-like Cells.
La Cognata, Valentina; D'Amico, Agata Grazia; Maugeri, Grazia; Morello, Giovanna; Guarnaccia, Maria; Magrì, Benedetta; Aronica, Eleonora; Alkon, Daniel L; D'Agata, Velia; Cavallaro, Sebastiano.
Afiliación
  • La Cognata V; Institute for Biomedical Research and Innovation, National Research Council, 95126 Catania, Italy.
  • D'Amico AG; Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Maugeri G; Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Morello G; Institute for Biomedical Research and Innovation, National Research Council, 95126 Catania, Italy.
  • Guarnaccia M; Institute for Biomedical Research and Innovation, National Research Council, 95126 Catania, Italy.
  • Magrì B; Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Aronica E; Department of (Neuro) Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 Amsterdam, The Netherlands.
  • Alkon DL; Synaptogenix, Inc., New York, NY 10036, USA.
  • D'Agata V; Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Cavallaro S; Institute for Biomedical Research and Innovation, National Research Council, 95126 Catania, Italy.
Int J Mol Sci ; 24(16)2023 Aug 15.
Article en En | MEDLINE | ID: mdl-37629005
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Esclerosis Amiotrófica Lateral / Corteza Motora Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / Esclerosis Amiotrófica Lateral / Corteza Motora Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza