ABSTRACT
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.
Subject(s)
Calcium/metabolism , Huntington Disease/diagnosis , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/metabolism , Disease Progression , Female , Homeostasis , Humans , Huntington Disease/genetics , Huntington Disease/metabolism , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , RNA, Messenger/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Vascular Endothelial Growth Factor A/geneticsABSTRACT
In 1906 Perusini began his scientific career publishing three papers. These articles were important for the understanding of degenerative dementia. Perusini studied the difference between Senile and Presenile Dementia. Emil Kraepelin distinguished its two forms, but Perusini didn't take a clear position because of his early heroic death on the slopes of Mount Sabotino on December in 1915.
