NEUROFILAMENTS

THE PRESENCE of linear fibrillar structures within nerve cells was first appreciated in the early part of the 19th century. The introduction of silver staining techniques made these structures readily apparent and many early theories of neuronal connectivity and conductivity involved them. From a medical point of view, the fibrils were seen to undergo an apparent thickening and increase in number in a variety of conditions including the human presenile dementia referred to as Alzheimer’s disease (TERRY, 1979). When ultrastructural methods became available it was discovered that the silver staining in normal neurons and in the toxic neuropathies was due to the presence of 8-9 nm dia. neurofilaments. The staining in Alzheimer’s disease was related to the presence of twisted fibrillar structures which have a maximum diameter of 19 nm. In this article we will concentrate on the normally-occurring neurofilament and return only briefly to the more specialized structures in Alzheimer’s disease and other human dementias. The use of histological and ultrastructural methods also indicated that astroglial cells in the vertebrate brain contain filaments which require silver techniques different from those of neurons for observation. These glial filaments are similar in appearance to, but thinner than, the neurofilaments (WUERKER, 1970). Other filaments of the ‘intermediate’ class (7-11 nm) have also been observed in a wide variety of non-neural cells and tissues (GASKIN & SHELANSKI, 1976). A pattern of replacement in the numbers of microtubules with neurofilaments has been observed with age in the rat optic nerve (PETERS & VAUGHN, 1967). In addition to this observation there was also a suggestion of a reciprocal relationship between the number of neurofilaments and microtubules in encephalopathy induced by mitotic spindle inhibitors (WISNIEWSKI et at., 1968). These observations led to the framing of three major questions: (a) What is the composition of the neurofilaments? (b) Does the reciprocal relationship in number of filaments and tubules indicate that they are polymorphic assembly forms of the same protein or that they are under reciprocal assembly control? (c) Are the proteins of intermediate filaments similar in different cell types and across species, as is the