ROLE OF THE PROTEIN QUALITY CONTOL SYSTEM IN MOTOR NEURON DISEASES: THE CASE OF MUSCLE CELLS
Tesi di Dottorato
Data di Pubblicazione:
2018
Citazione:
ROLE OF THE PROTEIN QUALITY CONTOL SYSTEM IN MOTOR NEURON DISEASES: THE CASE OF MUSCLE CELLS / M.e. Cicardi ; internal relator: A. Poletti ; coordinator: C. Sforza. DIPARTIMENTO DI SCIENZE FARMACOLOGICHE E BIOMOLECOLARI, 2018 Feb 06. 30. ciclo, Anno Accademico 2017. [10.13130/cicardi-maria-elena_phd2018-02-06].
Abstract:
Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA), are characterized by the progressive loss of motor neurons, and patients die for respiratory failure after the paralysis of voluntary muscle. Muscle system is, thus, highly affected but it is still unclear whether they play a role in disease onset or if they are a secondary target of toxicity. In my PhD period, I analyzed the behaviour in muscle cells of misfolded protein causing neurodegenerative diseases. I found that misfolded protein aggregates also in muscle cells. As a second step I studied the activation of the protein quality control system and its role at basal level in presence of misfolded proteins. I found that autophagy and proteasome are differently involved in the degradation of misfolded proteins in both muscle and motor neurons. Nevertheless, increasing the degradation of misfolded proteins by overexpressing key molecular chaperone or treating cells with autophagy inhibitors rescue the formation of aggregates in both models of disease.
Tipologia IRIS:
Tesi di dottorato
Keywords:
Motor neuron diseases; Protein misfolding; Protein quality control system; Autophagy; Muscle cells
Elenco autori:
M.E. Cicardi
Link alla scheda completa: