title: Changes of peripheral TGF-β1 depend on monocytes-derived macrophages in Huntington disease.
abstract: BACKGROUND
  Huntington Disease (HD) is a neurodegenerative disorder resulting from the expansion of polyglutamine stretch in the huntingtin protein (Htt). Mutant HTT (mHtt) leads to progressive impairment of several molecular pathways that have been linked to disease pathogenesis. Defects in the production of a number of neurotrophic factors have been described as important determinants contributing to the development of HD. We have previously demonstrated that production of transforming growth factor-β1 (TGF-β1) is also deregulated in HD. Peripheral levels of TGF-β1 were markedly reduced early in the disease and returned to normal levels with disease severity. However, the cause and the biochemical origin of such abnormalities are still unclear.
  
  
  RESULTS
  We report here that the abnormal production of peripheral TGF-β1 depends on the changes in the percentage of TGF-β1-producing macrophages along disease course. Variation in the number of TGF-β1-producing macrophages resulted from differential activation state of the same cells, which displayed phenotypic and functional heterogeneity throughout the clinical course of HD. We further demonstrated that, similar to the periphery, the number of TGF-β1-immunoreactive cells in human post-mortem brain with HD, varied with neuropathological changes.
  
  
  CONCLUSIONS
  Our data indicate that reduced bioavailability of TGF-β1 in the serum of HD subjects is attributable to the variation of the number of TGF-β1-producing macrophages. Macrophages display a differential ability to produce TGF-β1, which reflects diversity in cells polarization throughout the disease course. Besides elucidating the biochemical origin of TGF-β1 fluctuations in HD, our study highlights an interesting parallelism between periphery and central compartment and underlines the potential of TGF-β1 as a possible indicator suitable for prediction of disease onset in HD.
authors: Alba
authors: A
authors: Di Pardo
authors: Silvia
authors: S
authors: Alberti
authors: Vittorio
authors: V
authors: Maglione
authors: Enrico
authors: E
authors: Amico
authors: Etty P
authors: EP
authors: Cortes
authors: Francesca
authors: F
authors: Elifani
authors: Giuseppe
authors: G
authors: Battaglia
authors: Carla L
authors: CL
authors: Busceti
authors: Ferdinando
authors: F
authors: Nicoletti
authors: Jean Paul G
authors: JP
authors: Vonsattel
authors: IRCCS Neuromed, 86077 Pozzilli, Italy. ferdinando.squitieri@lirh.it.
authors: Ferdinando
authors: F
authors: Squitieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D016764:Cell Polarity; D003710:Demography; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
chemical_list: C508960:TGFB1 protein, human; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1