Degeneration and death of neurons in adult neurodegenerative diseases

作者：Sarkar PK^*

来源：Current Science, 2005, 89(5): 764-773.

• multifunctional drugs
• neurodegenerative diseases
• neuronal death
• oxidative stress
• protein aggregation

Biochemical and biophysical events responsible for the degeneration and death of neurons in some common adult neurodegenerative diseases have been discussed. Critical analysis suggests that although aberrant aggregation of the diseased proteins represents an important factor in some instances, oxidative stress is probably the mother of most of the crucial events responsible for cell death, since it not only contributes to protein aggregation but also induces two other phenomena, viz. mitochondrial dysfunction and glutamate excitotoxicity, which play an important role in the death of neurons. Excellent reviews on oxidative stress, protein aggregation and mitochondrial dysfunction have appeared recently. Here, the discussion is focused on the relative contribution and interrelationship between the critical events, which are responsible for the ultimate demise of neurons. Based on the knowledge of the critical steps of the death pathway of neurons, current strategies for the development of potentially important multifunctional drugs, which are under clinical trial, have been reviewed. These new drugs target multiple steps in the cascade of the death pathway of neurons and are expected to be far more effective in dealing with these as yet incurable and inexorable diseases.

• 出版日期2005-9-10