title: Targeting ubiquilin-1 in Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a common neurodegenerative disorder affecting an increasing number of people worldwide as the population ages. Currently, there are no drugs available that could prevent AD pathogenesis or slow down its progression. Increasing evidence links ubiquilin-1, an ubiquitin-like protein, into the pathogenic mechanisms of AD and other neurodegenerative diseases. Ubiquilin-1 has been shown to play a key role in the regulation of the levels, subcellular targeting, aggregation and degradation of various neurodegenerative disease-associated proteins. These include the amyloid precursor protein and presenilins that are intimately involved in the mechanisms of AD.
  
  
  METHODS
  Here, the properties and diverse functions of ubiquilin-1 protein in the context of the pathogenesis of AD and other neurodegenerative disorders are discussed. This review recapitulates the available knowledge on the involvement of ubiquilin-1 in the genetic and molecular mechanisms in AD. Furthermore, the association of ubiquilin-1 with specific proteins and mechanisms involved in the pathogenesis of neurodegenerative diseases is described and the known ubiquilin-1-interacting proteins summarized.
  
  
  CONCLUSIONS
  The variety of ubiquilin-1-interacting proteins and its central role in the regulation of protein levels and degradation provides a number of novel candidates and approaches for future research and drug discovery.
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Takalo
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.forename: Teemu
authors.initials: T
authors.lastname: Natunen
authors.forename: Jayashree
authors.initials: J
authors.lastname: Viswanathan
authors.forename: Kaisa Ma
authors.initials: KM
authors.lastname: Kurkinen
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C107792:UBQLN1 protein, human