title: Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer's disease.
abstract: Recent new findings indicate significant biological roles of cysteine cathepsin proteases in secretory vesicles for production of biologically active peptides. Notably, cathepsin L in secretory vesicles functions as a key protease for proteolytic processing of proneuropeptides (and prohormones) into active neuropeptides that are released to mediate cell-cell communication in the nervous system for neurotransmission. Moreover, cathepsin B in secretory vesicles has been recently identified as a β-secretase for production of neurotoxic β- amyloid (Aβ) peptides that accumulate in Alzheimer's disease (AD), participating as a notable factor in the severe memory loss in AD. These secretory vesicle functions of cathepsins L and B for production of biologically active peptides contrast with the well-known role of cathepsin proteases in lysosomes for the degradation of proteins to result in their inactivation. The unique secretory vesicle proteome indicates proteins of distinct functional categories that provide the intravesicular environment for support of cysteine cathepsin functions. Features of the secretory vesicle protein systems insure optimized intravesicular conditions that support the proteolytic activity of cathepsins. These new findings of recently discovered biological roles of cathepsins L and B indicate their significance in human health and disease. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, Dept. of Neurosciences, Univ. of Calif., San Diego, USA. vhook@ucsd.edu
authors.forename: Vivian
authors.initials: V
authors.lastname: Hook
authors.forename: Lydiane
authors.initials: L
authors.lastname: Funkelstein
authors.forename: Jill
authors.initials: J
authors.lastname: Wegrzyn
authors.forename: Steven
authors.initials: S
authors.lastname: Bark
authors.forename: Mark
authors.initials: M
authors.lastname: Kindy
authors.forename: Gregory
authors.initials: G
authors.lastname: Hook
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002401:Cathepsin B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D056668:Cathepsin L / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002403:Cathepsins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D057056:Cysteine Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D059748:Proteolysis; D022142:Secretory Vesicles / Q000201:enzymology / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents; D010455:Peptides; D002403:Cathepsins; D057056:Cysteine Proteases; D002401:Cathepsin B; D056668:Cathepsin L