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Niacin, an innovative protein kinase-C-dependent endoplasmic reticulum stress reticence in murine Parkinson's disease.
Roshdy, Merna; Zaky, Doaa A; Abbas, Samah S; Abdallah, Dalaal M.
Afiliación
  • Roshdy M; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Ahmed Orabi District, Cairo 44971, Egypt.
  • Zaky DA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Electronic address: doaa.zaky@pharma.cu.edu.eg.
  • Abbas SS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Ahmed Orabi District, Cairo 44971, Egypt.
  • Abdallah DM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
Life Sci ; 351: 122865, 2024 Aug 15.
Article en En | MEDLINE | ID: mdl-38914304
ABSTRACT

AIMS:

Niacin (NIA) supplementation showed effectiveness against Parkinson's disease (PD) in clinical trials. The depletion of NAD and endoplasmic reticulum stress response (ERSR) are implicated in the pathogenesis of PD, but the potential role for NAD precursors on ERSR is not yet established. This study was undertaken to decipher NIA molecular mechanisms against PD-accompanied ERSR, especially in relation to PKC.

METHODS:

Alternate-day-low-dose-21 day-subcutaneous exposure to rotenone (ROT) in rats induced PD. Following the 5th ROT injection, rats received daily doses of either NIA alone or preceded by the PKC inhibitor tamoxifen (TAM). Extent of disease progression was assessed by behavioral, striatal biochemical and striatal/nigral histopathological/immunohistochemical analysis. KEY

FINDINGS:

Via activating PKC/LKB1/AMPK stream, NIA post-treatment attenuated the ERSR reflected by the decline in ATF4, ATF6 and XBP1s to downregulate the apoptotic markers, CHOP/GADD153, p-JNK and active caspase-3. Such amendments congregated in motor activity/coordination improvements in open field and rotarod tasks, enhanced grid test latency and reduced overall PD scores, while boosting nigral/striatal tyrosine hydroxylase immunoreactivity and increasing intact neurons (Nissl stain) in both SNpc and striatum that showed less neurodegeneration (H&E stain). To different extents, TAM reverted all the NIA-related actions to prove PKC as a fulcrum in conveying the drug neurotherapeutic potential.

SIGNIFICANCE:

PKC activation is a pioneer mechanism in the drug ERSR inhibitory anti-apoptotic modality to clarify NIA promising clinical and potent preclinical anti-PD efficacy. This kinase can be tagged as a druggable target for future add-on treatments that can assist dopaminergic neuronal aptitude against this devastating neurodegenerative disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés del Retículo Endoplásmico / Niacina Límite: Animals Idioma: En Revista: Life Sci Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés del Retículo Endoplásmico / Niacina Límite: Animals Idioma: En Revista: Life Sci Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos