Neurofilaments in Aged Animals.

Neurofilaments (NFs) are neuronal intermediate filaments assembled mainly from three subunit proteins, NF-L, NF-M and NF-H. NFs are the major cytoskeletal element of axons, particularly large myelinated axons. Accumulation of NFs in the cell body or proximal axons is a hallmark of motor neuron diseases, of which aging is a risk factor. It is not known whether the accumulation of NFs is the primary causative factor of these diseases; however, it is feasible that accumulated NFs are obstacles for axonal trafficking, resulting in a decreased supply of proteins and organelles required for the maintenance of or activity in the distal axons. Axonal transport of NFs slows down with aging and the decreased rate of transport could be a risk factor for disease. Therefore, it is important to determine age-dependent changes in properties of NFs. In this chapter we review the characteristics of NFs in aged animals. The most striking morphological change in NFs is their density within axons. NFs are more than twice as densely packed in the proximal region of aged rat sciatic nerve axons compared with those in young adult rats. A remarkable biochemical change is the reduction of NF-M content in aged NFs. This is partly because of the reduced transcription of NF-M in aged rats. The relationship between NF packing and reduced NF-M is discussed in terms of the age-dependent decrease in axonal transport and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]