Inhibition of neuronal apoptosis by the cyclin‐dependent kinase inhibitor GW8510: Identification of 3′ substituted indolones as a scaffold for the development of neuroprotective drugs

• Published in: Journal of neurochemistry Vol. 93; no. 3; pp. 538 - 548
• Main Authors: Johnson, Kyle, Liu, Li, Majdzadeh, Nazanin, Chavez, Cindy, Chin, Paul C., Morrison, Brad, Wang, Lulu, Park, Jane, Chugh, Priti, Chen, Hsin‐Mei, D'Mello, Santosh R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2005; Blackwell
• Subjects: 3′ substituted indolones; Ageing, cell death; Animals; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Cell Line; Cell physiology; cerebellar granule neurons; Cyclin-Dependent Kinases - antagonists & inhibitors; Cyclin-Dependent Kinases - metabolism; cyclin‐dependent kinases; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Indoles - chemistry; Indoles - pharmacology; Medical sciences; Molecular and cellular biology; neurodegeneration; neuronal apoptosis; Neurons - drug effects; Neurons - enzymology; Neuropharmacology; neuroprotection; Neuroprotective agent; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Pharmacology. Drug treatments; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Wistar; Human; Drug; 3' substituted indolones; Extracellular signal-regulated protein kinase; Granule neuron; Enzyme; Central nervous system; Akt protein kinase; neurodegeneration; Activation; In vitro; Cyclin-dependent kinase 5; neuronal apoptosis; Encephalon; Cyclin-dependent kinase; cerebellar granule neurons; Treatment; cyclin-dependent kinases; Cell death; neuroprotection; Cell cycle; Development; Potassium; Apoptosis

Increasing evidence suggests that neuronal apoptosis is triggered by the inappropriate activation of cyclin‐dependent kinases leading to an abortive re‐entry of neurons into the cell cycle. Pharmacological inhibitors of cell‐cycle progression may therefore have value in the treatment of neurodegener...