Collagen XVII in the Human Brain

Collagens have previously been overlooked for roles in the brain since fibrillar collagens, the best known and most widely studied example of collagens, are not present in the mature central nervous system (CNS). However, over the last decade it has become increasingly apparent that collagens are not merely structural proteins giving strength to tissue, but bio-active molecules with a dynamic role within the CNS. In fact, a role in the CNS, albeit often transient, has been identified for nearly every type of collagen during some phase of CNS development. Thus, collagens are now thought to have a decisive role in various aspects of neural maturation and are currently being studied in relation to various neurological disorders. Collagen XVII is one of the four non-fibril-forming transmembrane collagens, which function as both matrix proteins and cell-surface receptors. It is known to be a structural component of hemidesmosomes, which mediate adhesion of epidermal keratinocytes and certain other epithelial cells to the underlying basement membrane. Based on numerous case, animal and epidemiological studies, collagen XVII could be one of the most interesting putative antigens common to both dermatological and neurological disease. In this thesis, collagen XVII was studied in the mature human brain, using brain samples obtained at autopsy and an array of standard histological and molecular research methods. The aim was to establish whether collagen XVII is present in the human central nervous system and if so, to define the anatomical regions, cells and intracellular locations in which it is expressed. Also, possible changes in expression due to motor neuron disease-related neuropathology, as visualized with p62, were studied. This study found that collagen XVII is expressed in human CNS neurons and that it is widely distributed in different anatomical regions of the human brain. Intraneuronally, the immunoreactivity is localised to lipofuscin granules. The study also established that the expression of collagen XVII is not altered in motor neuron disease and that the presence of p62positive inclusions outside the motor system in motor neuron disease could be a marker for psychiatric morbidity. National Library of Medical Classification: QW 504.5, QZ 35, WE 550, WL 300 Medical Subject Headings: Collagen Type XVII; Non-Fibrillar Collagens; Central Nervous System; Immunohistochemistry; Lipofuscin; Motor Neuron Disease; Autopsy; Brain; Humans