Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease.
Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington's disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and age-matched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and pre-manifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD.
Dipartimento di Scienze Mediche e Biologiche, Università degli Studi di Udine, Udine, Italy.
Federica
F
Cesca
SOC Istituto di Genetica, Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Elisa
E
Bregant
Clinical Institute of Medical Genetics, University Medical Centre, Ljubljana, Slovenia.
Borut
B
Peterlin
Clinical Institute of Medical Genetics, University Medical Centre, Ljubljana, Slovenia; Community Health Centre Ljubljana, Metelkov, Ljubljana, Slovenia.
Maja
M
Zadel
Dipartimento di Scienze Mediche e Biologiche, Università degli Studi di Udine, Udine, Italy.
Giorgia
G
Dubsky de Wittenau
Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Pisa, Pisa, Italy.
Gabriele
G
Siciliano
Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Pisa, Pisa, Italy.
Roberto
R
Ceravolo
Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Pisa, Pisa, Italy.
Lucia
L
Petrozzi
Clinica Neurologica Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Giada
G
Pauletto
Clinica Neurologica Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Lorenzo
L
Verriello
Clinica Neurologica Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Paolo
P
Bergonzi
SOC Istituto di Genetica, Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Giuseppe
G
Damante
Medicina Trasfusionale, Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Giovanni
G
Barillari
Neurologia, Azienda Ospedaliera, Santa Maria degli Angeli, Pordenone, Italy.
Bruno
B
Lucci
Dipartimento di Scienze Mediche e Biologiche, Università degli Studi di Udine, Udine, Italy; SOC Istituto di Patologia Clinica, Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Francesco
F
Curcio
Dipartimento di Scienze Mediche e Biologiche, Università degli Studi di Udine, Udine, Italy; SOC Istituto di Patologia Clinica, Azienda Ospedaliero Universitaria di Udine, Udine, Italy.
Incoronata Renata
IR
Lonigro
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006706:Homeostasis; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium