Cytoskeltal intermediate filaments in Tau pathology and neurodegeneration

Intermediate filaments are cytoskeletal proteins that are vital for proper cell structure formation and functioning. There are six types of these proteins. Type I includes acidic keratins, Type II includes basic and neutral keratins, both of which are present in epithelial cells. Type III includes vimentin, desmin, glial fibrillary acidic protein and peripherin, among which the last two are highly involved in neurodegenerative diseases. Type IV includes three types of neurofilament proteins, NF-L, NF-M and NF-H, where L signifies light, M signifies medium and H signifies heavy. The fourth protein in this category is α-internexin. All of these proteins are highly involved in neurodegenerative diseases, especially the neurofilament proteins. The type V intermediate filament proteins are lamins. The type VI intermediate filaments are nestins. Their involvement in a variety of neurodegenerative diseases has been observed, including Alzheimer's disease, Cerebral Ischemia, Multiple Sclerosis, Alexander Disease, Neuronal IF inclusion disease (NIFID) and Amyotrophic Lateral Sclerosis (ALS). Alzheimer's disease is a neurodegenerative disease in which two proteins are mainly involved, the Tau protein and the Amyloid-β protein. This review discusses the crosstalk of the intermediate filament proteins with the pathological proteins involved in the neurodegenerative diseases. For the case of the Alzheimer's disease, many of the intermediate filament proteins are involved in the disease pathology and are vital markers for the disease. One of the category of proteins involved is neurofilaments, among which NF-L is a marker for the disease. Keratin 9 and the glial fibrillary acidic protein (GFAP) are other intermediate filament proteins that are being explored as markers for the Alzheimer's disease.