RT Journal Article
T1 Autophagy Alteration in ApoA-I Related Systemic Amyloidosis
A1 Giudice, Rita Del
A1 Imbimbo, Paola
A1 Pietrocola, Federico
A1 Martins, Isabelle
A1 De Palma, Fatima Domenica Elisa
A1 Bravo San Pedro, José Manuel
A1 Kroemer, Guido
A1 Maiuri, Maria Chiara
A1 Monti, Daria Maria
AB Amyloidoses are characterized by the accumulation and aggregation of misfolded proteins into fibrils in different organs, leading to cell death and consequent organ dysfunction. The specific substitution of Leu 75 for Pro in Apolipoprotein A-I protein sequence (ApoA-I; L75P-ApoA-I) results in late onset amyloidosis, where deposition of extracellular protein aggregates damages the normal functions of the liver. In this work, we describe that the autophagic process is inhibited in the presence of the L75P-ApoA-I amyloidogenic variant in stably transfected human hepatocyte carcinoma cells. The L75P-ApoA-I amyloidogenic variant alters the redox status of the cells, resulting into excessive mitochondrial stress and consequent cell death. Moreover, L75P-ApoA-I induces an impairment of the autophagic flux. Pharmacological induction of autophagy or transfection-enforced overexpression of the pro-autophagic transcription factor EB (TFEB) restores proficient proteostasis and reduces oxidative stress in these experimental settings, suggesting that pharmacological stimulation of autophagy could be a promising target to alleviate ApoA-I amyloidosis.
PB MPDI
SN 1422-0067
YR 2022
FD 2022-03-23
LK https://hdl.handle.net/20.500.14352/71740
UL https://hdl.handle.net/20.500.14352/71740
LA eng
DS Docta Complutense
RD 5 abr 2025