Harmaline, an alcaloid of Paganum Armala, induces tremors of central origin and increases cerebellar cGMP without affecting cortical and cerebellar prostaglandin levels. 16(S)-16-methyl PGE2 protects the animals against the seizures induced by the alcaloid and prevents the concomitant rise in cerebellar cGMP. Experiment performed in cats and limited to pharmacological observations, confirmed that, the PGE2 derivative, is a powerful antitremorogenic agent at doses that are devoid of appreciable side effects.
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http://dx.doi.org/10.1016/0090-6980(78)90153-3 | DOI Listing |
EMBO J
January 2025
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
November 2024
Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Chaumuhan, Mathura, India.
Zhejiang Da Xue Xue Bao Yi Xue Ban
June 2024
School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China.
Phosphodiesterases (PDE) are involved in the regulation of cellular physiological processes and neurological functions, including neuronal plasticity, synapto-genesis, synaptic transmission, memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system (CNS) diseases by inhibiting cAMP hydrolysis, increasing cAMP content and enhancing its downstream effects. PDE4 inhibitors have long-term potentiation effect, which can enhance phosphorylation of cAMP response element binding protein (CREB) and upregulate expression of memory related Arc genes in hippocampal neurons, thereby improving cognitive impairment and Alzheimer's disease-like symptoms.
View Article and Find Full Text PDFRedox Biol
April 2024
Aging Neuroscience Research Team, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, 173-0015, Japan. Electronic address:
Although reactive oxygen species (ROS) are known to have harmful effects in organisms, recent studies have demonstrated expression of ROS synthases at various parts of the organisms and the controlled ROS generation, suggesting possible involvement of ROS signaling in physiological events of individuals. However, physiological roles of ROS in the CNS, including functional roles in higher brain functions or neuronal activity-dependent ROS production, remain to be elucidated. Here, we demonstrated involvement of ROS - 8-NO-cGMP signaling in motor learning and synaptic plasticity in the cerebellum.
View Article and Find Full Text PDFCell Rep
September 2023
Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Southeast Louisiana VA Healthcare System, New Orleans, LA 70119, USA. Electronic address:
While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior. However, the mechanisms that underlie learning-induced changes in intrinsic excitability during memory formation are poorly understood. In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation.
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