title: Nuclear receptors as therapeutic targets for Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is characterized by the accumulation and extensive deposition of amyloid β (Aβ) in the parenchyma of the brain. This accumulation of amyloid is associated with perturbations in synaptic function, impairments in energy metabolism and induction of a chronic inflammatory response which acts to promote neuronal loss and cognitive impairment.
  
  
  METHODS
  Currently, there are no drugs that target the underlying mechanisms of AD. Here, we propose a class of nuclear receptors as novel and promising new therapeutic targets for AD. This review summarizes the literature on nuclear receptors and their effects on AD-related pathophysiology.
  
  
  CONCLUSIONS
  Nuclear receptors are attractive targets for the treatment of AD due to their ability to facilitate degradation of Aβ, affect microglial activation and suppress the inflammatory milieu of the brain. Liver X receptor agonists have proven difficult to move into clinical trials as long-term treatment results in hepatic steatosis. It is our view that PPAR-γ activation remains a promising avenue for the treatment for AD; however, the poor BBB permeability of the currently available agonists and the negative outcome of the Phase III clinical trials are likely to diminish interest in pursuing this target.
authors: Case Western Reserve University School of Medicine, Department of Neurosciences, Alzheimer Research Laboratory, Cleveland, OH 44106, USA.
authors: Shweta
authors: S
authors: Mandrekar-Colucci
authors: Gary E
authors: GE
authors: Landreth
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000503:physiopathology; D016503:Drug Delivery Systems; D015195:Drug Design; D004734:Energy Metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D017628:Microglia / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018160:Receptors, Cytoplasmic and Nuclear