During the last 5 or 6 years fundamental new insights into the role of the neural cytoskeleton have emerged. These findings have completely changed our perception of the cytoskeleton as a potential target for therapeutic intervention in neurological diseases. A short list of the most pertinent findings in my view:
- We know that mutations in genes encoding neural cytoskeleton components can cause severe developmental problems in the human CNS (for example, mutations in tubulin genes TUBA3 and TUBB3, in the gene for the microtubule-associated protein Tau (MAPT), and in genes encoding the microtubule motor associated regulators doublecortin and Lis1). These mutations lead to mental retardation in humans, underlining the importance of proper function of the neural cytoskeleton.
- Neural cytoskeleton components are involved in psychiatric disorders (for example, microtubule regulators in schizophrenia).
- Neural cytoskeleton components are involved in neurodegenerative diseases (for example, the microtubule-associated protein Tau in Alzheimer’s disease).
- The proper function of the neuronal cytoskeleton is essential for regenerative processes after injury in the peripheral and central nervous system.
- Finally and perhaps most importantly, therapeutic targeting of neural cytoskeleton components by drugs can have beneficial effects. Probably the most dramatic examples are the positive effects of drug-induced stabilization of microtubules in axon regeneration and in a mouse model of schizophrenia.
In my view these findings more than justify a strong commitment to further research. The initial goals of these activities could be
- extended efforts to identify links between additional neurodegenerative and psychiatric disorders and the cytoskeleton
- a deeper understanding of the molecular mechanisms involved, for example, the molecular and cell biological consequences of changes in microtubule and F-actin dynamics, the role of posttranslational modifications of tubulin, actin and associated proteins, and the regulation of the activity of cytoskeletal-associated proteins
- the development of new drugs to interfere with cytoskeletal functions that are either more suitable for use in humans than existing ones or specifically target cytoskeletal components that have so far eluded intervention such as specific microtubule- or actin-associated proteins or motor proteins.