Experimental evidences indicate how the σ1 receptor is involved in several fundamental processes for cell survival. In ALS, the possible overexpression of truncated isoforms of σ1 missing the portion that allows the activity of chaperone could, by acting in monomeric form or by binding to the canonical form, destabilize the receptor for IP3, reduce the flows of Ca2 + between ER and mitochondria and decrease the availability of ATP favoring apoptosis and autophagy. Since no selective biological markers are yet available to diagnose and / or monitor the progress of ALS, currently, the diagnosis is formulated exclusively on the basis of clinical criteria. In this work we wanted to evaluate the presence of the σ1 truncated isoform (σ1short or hSIG-1SR) in mononuclear leukocytes and autopsy specimens from ALS patients and verify if the expression levels of σ1 canonical (hSIG-1) and σ1short were altered compared to healthy subjects. The choice to use peripheral blood cells arises from the attempt to identify characteristic features of ALS and find selective human biological markers in cells available with minimally invasive methods, to allow the diagnosis and monitoring of ALS. However, because lymphocytes may not reflect the possible role played by truncated σ1 receptor isoforms in areas of the central nervous system such as motoneurons, which are selectively affected by the disease, the same study was also performed on autoptic spinal cord of patients with ALS. In both cases, no significant differences were observed in the parameters evaluated between healthy controls and ALS patients.
Diverse evidenze sperimentali, indicano come il recettore σ1 sia coinvolto in numerosi processi fondamentali per la sopravvivenza della cellula. Nella SLA, la possibile sovraespressione di isoforme tronche del recettore mancanti della porzione che permette l’attività di chaperone potrebbe, agendo in forma monomerica o legandosi alla forma canonica, destabilizzare il recettore per IP3, ridurre i flussi di Ca2+ fra RE e mitocondri e diminuire la disponibilità di ATP favorendo l'apoptosi e l’autofagia. Non essendo ancora disponibili marcatori biologici selettivi per diagnosticare e/o monitorare l’andamento della SLA, attualmente, la diagnosi è formulata esclusivamente sulla base di criteri clinici. In questo lavoro si è voluto valutare la presenza dell’isoforma σ1 tronca (σ1short o hSIG-1SR) in leucociti mononucleati e campioni di midollo spinale autoptico appartenenti a pazienti affetti da SLA e verificare se i livelli di espressione di σ1 canonica (hSIG-1) e σ1short fossero alterati rispetto ai soggetti sani. La scelta di utilizzare cellule di sangue periferico nasce dal tentativo di individuare tratti caratteristici della SLA e trovare marcatori biologici selettivi in cellule umane reperibili con metodi poco invasivi, per consentire la diagnosi e il monitoraggio dell’andamento della SLA. Tuttavia, poiché i linfociti potrebbero non rispecchiare il possibile ruolo giocato da isoforme tronche del recettore σ1 in aree del sistema nervoso centrale come i motoneuroni, che sono selettivamente colpiti dalla patologia, lo stesso studio è stato condotto anche su midollo spinale autoptico di pazienti affetti da SLA. In entrambi i casi, non si osservano differenze significative nei parametri valutati tra controlli sani e pazienti SLA.
Valutazione di un’isoforma tronca del recettore Sigma 1 (hSIGMA-1SR) come possibile biomarker di sclerosi laterale amiotrofica (SLA) in leucociti mononucleati e midollo spinale autoptico di pazienti affetti dalla patologia.
FORZA, KEVIN
2017/2018
Abstract
Experimental evidences indicate how the σ1 receptor is involved in several fundamental processes for cell survival. In ALS, the possible overexpression of truncated isoforms of σ1 missing the portion that allows the activity of chaperone could, by acting in monomeric form or by binding to the canonical form, destabilize the receptor for IP3, reduce the flows of Ca2 + between ER and mitochondria and decrease the availability of ATP favoring apoptosis and autophagy. Since no selective biological markers are yet available to diagnose and / or monitor the progress of ALS, currently, the diagnosis is formulated exclusively on the basis of clinical criteria. In this work we wanted to evaluate the presence of the σ1 truncated isoform (σ1short or hSIG-1SR) in mononuclear leukocytes and autopsy specimens from ALS patients and verify if the expression levels of σ1 canonical (hSIG-1) and σ1short were altered compared to healthy subjects. The choice to use peripheral blood cells arises from the attempt to identify characteristic features of ALS and find selective human biological markers in cells available with minimally invasive methods, to allow the diagnosis and monitoring of ALS. However, because lymphocytes may not reflect the possible role played by truncated σ1 receptor isoforms in areas of the central nervous system such as motoneurons, which are selectively affected by the disease, the same study was also performed on autoptic spinal cord of patients with ALS. In both cases, no significant differences were observed in the parameters evaluated between healthy controls and ALS patients.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/25207