Application of ubiquitin immunohistochemistry to the diagnosis of disease.
Ubiquitin immunohistochemistry has changed understanding of the pathophysiology of many diseases, particularly chronic neurodegenerative diseases. Protein aggregates (inclusions) containing ubiquitinated proteins occur in neurones and other cell types in the central nervous system in afflicted cells. The inclusions are present in all the neurological illnesses, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, polyglutamine diseases, and rarer forms of neurodegenerative disease. A new cause of cognitive decline in the elderly, "dementia with Lewy bodies," accounting for some 15-30% of cases, was initially discovered and characterized by ubiquitin immunocytochemistry. The optimal methods for carrying out immunohistochemical analyses of paraffin-embedded tissues are described, and examples of all the types of intracellular inclusions detected by ubiquitin immunohistochemistry in the diseases are illustrated. The role of the ubiquitin proteasome system (UPS) in disease progression is being actively researched globally and increasingly, because it is now realized that the UPS controls most pathways in cellular homeostasis. Many of these regulatory mechanisms will be dysfunctional in diseased cells. The goal is to understand fully the role of the UPS in the disorders and then therapeutically intervene in the ubiquitin pathway to treat these incurable diseases.
Lowe
James
J
School of Molecular Medical Sciences, University of Nottingham Medical School, Queens Medical Centre, Nottingham, United Kingdom.
Hand
Neil
N
Mayer
R John
RJ
D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism; D000906:Antibodies / Q000276:immunology; D001369:Axons; D003933:Diagnosis; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000175:diagnosis / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D018911:Trinucleotide Repeats; D025801:Ubiquitin / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D025801:Ubiquitin