Cytoskeletal protein abnormalities in neurodegenerative diseases

The nervous system is a rich source of filamentous proteins that assume critical roles in determining and maintaining neuronal form and function. Neurons contain three major classes of these cytoskeletal organelles: microtubules, intermediate filaments, and microfilaments. They also contain a variety of proteins that organize them and serve to connect them with each other. Such major neurodegenerative diseases as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as a variety of toxic neuropathies, are characterized pathologically by intraneuronal filamentous inclusions. Recent studies using biochemical and immunocytochemical techniques have established that these abnormalities represent disorganized states of the neuronal cytoskeleton and have determined some of the specific molecular constituents of these inclusions. This knowledge has led to new ways of thinking about their origins.