Huntington's Disease is an inherited neurodegenerative disease that affects the medium spiny neurons in the striatum. The disease is caused by the expansion of a polyglutamine sequence in the N terminus of Huntingtin (Htt), a widely expressed protein. Recently, we have found that Htt is an antiapoptotic protein in striatal cells and acts by preventing caspase-3 activity. Here we report that Htt overexpression in other CNS-derived cells can protect them from more than 20 days exposure to fatal stimuli. In particular, we found that cytochrome c continues to be released from mitochondria into the cytosol of cells that overexpress normal Htt. However, procaspase-9 is not processed, indicating that wild-type Htt (wtHtt) acts downstream of cytochrome c release. These data show that Htt inhibits neuronal cell death by interfering with the activity of the apoptosome complex.

Huntingtin’s neuroprotective activity occurs via inhibition of pro-caspase 9 processing / D. Rigamonti, S. Sipione, D. Goffredo, C. Zuccato, E. Fossale, E. Cattaneo. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 276:18(2001), pp. 14545-14548. [10.1074/jbc.C100044200]

Huntingtin’s neuroprotective activity occurs via inhibition of pro-caspase 9 processing

D. Rigamonti
Primo
;
D. Goffredo;C. Zuccato;E. Cattaneo
Ultimo
2001

Abstract

Huntington's Disease is an inherited neurodegenerative disease that affects the medium spiny neurons in the striatum. The disease is caused by the expansion of a polyglutamine sequence in the N terminus of Huntingtin (Htt), a widely expressed protein. Recently, we have found that Htt is an antiapoptotic protein in striatal cells and acts by preventing caspase-3 activity. Here we report that Htt overexpression in other CNS-derived cells can protect them from more than 20 days exposure to fatal stimuli. In particular, we found that cytochrome c continues to be released from mitochondria into the cytosol of cells that overexpress normal Htt. However, procaspase-9 is not processed, indicating that wild-type Htt (wtHtt) acts downstream of cytochrome c release. These data show that Htt inhibits neuronal cell death by interfering with the activity of the apoptosome complex.
Settore BIO/14 - Farmacologia
2001
Article (author)
File in questo prodotto:
File Dimensione Formato  
Rigamonti JBC 2001.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 235.35 kB
Formato Adobe PDF
235.35 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/209315
Citazioni
  • ???jsp.display-item.citation.pmc??? 35
  • Scopus 136
  • ???jsp.display-item.citation.isi??? 126
social impact