title: Lysosomal cathepsins and their regulation in aging and neurodegeneration.
abstract: Lysosomes and lysosomal hydrolases, including the cathepsins, have been shown to change their properties with aging brain a long time ago, although their function was not really understood. The first biochemical and clinical studies were followed by a major expansion in the last 20 years with the development of animal disease models and new approaches leading to a major advancement of understanding of the role of physiological and degenerative processes in the brain at the molecular level. This includes the understanding of the major role of autophagy and the cathepsins in a number of diseases, including its critical role in the neuronal ceroid lipofuscinosis. Similarly, cathepsins and some other lysosomal proteases were shown to have important roles in processing and/or degradation of several important neuronal proteins, thereby having either neuroprotective or harmful roles. In this review, we discuss lysosomal cathepsins and their regulation with the focus on cysteine cathepsins and their endogenous inhibitors, as well as their role in several neurodegenerative diseases.
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Jamova 39, Sl-1000 Ljubljana, Slovenia; J. Stefan International Postgraduate School, Jamova 39, Sl-1000 Ljubljana, Slovenia. Electronic address: veronika.stoka@ijs.si.
authors.forename: Veronika
authors.initials: V
authors.lastname: Stoka
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Jamova 39, Sl-1000 Ljubljana, Slovenia; J. Stefan International Postgraduate School, Jamova 39, Sl-1000 Ljubljana, Slovenia.
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, Jamova 39, Sl-1000 Ljubljana, Slovenia; Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova 39, Sl-1000 Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, Sl-1000 Ljubljana, Slovenia. Electronic address: boris.turk@ijs.si.
authors.forename: Boris
authors.initials: B
authors.lastname: Turk
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D002403:Cathepsins / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002403:Cathepsins
keywords: Aging; Alzheimer's disease; Cathepsin D; Cystatin; Cysteine cathepsin; EPM-1; Neuronal ceroid lipofuscinosis