title: Alterations in Activity-Dependent Neuroprotective Protein in Sporadic and Experimental Parkinson's Disease.
abstract: BACKGROUND
  Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and neuronal survival. It is possible that intracellular alpha-synuclein (α-syn) inclusions may be due to, or may cause, down-regulation of ADNP expression.
  
  
  OBJECTIVE
  This study were to determine whether ADNP protein levels are altered in nigral dopaminergic neurons, establish whether ADNP alterations are associated with α-syn accumulation, and evaluate potential correlations between levels of ADNP expression and axonal transport motor proteins in sporadic and experimental Parkinson's disease (PD).
  
  
  METHODS
  Twenty human brains from PD (n = 12) and age-matched controls (n = 8) and sixteen rat brains received α-synuclein gene (n = 8) or empty vector (n = 8) were analyzed using immunohistochemistry. The number of ADNP labeled nigral neurons were estimated with stereology and the levels of ADNP were determined using densitometry.
  
  
  RESULTS
  Compared to age-matched controls, a marked reduction in ADNP protein levels was observed in neuromelanin-containing nigral neurons of PD. Reduced ADNP levels did no relate to the progression of PD symptoms, but instead occurred at early PD stages, before reductions in tyrosine hydroxylase could be detected. Reductions in ADNP were also positively correlated with alterations in axonal transport motor protein. Reductions in ADNP levels were recapitulated in a rat model of PD based on viral over-expression of human wild-type α-synuclein, suggesting that ADNP reductions in PD are a direct result of α-synuclein overexpression.
  
  
  CONCLUSIONS
  These findings demonstrate that the down-regulation of protein ADNP is an early pathological alteration and may contribute to dopaminergic neurodegeneration in PD.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Gerardo A
authors.initials: GA
authors.lastname: Morfini
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Kordower
mesh_terms: D000818:Animals; D001344:Autopsy; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: C492178:ADNP protein, human; C579795:ADNP protein, rat; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein
keywords: Activity-dependent neuroprotective protein; Parkinson’s disease; axonal transport; synucleinopathy