Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer's Disease patients: a pilot study

Abstract

Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer’s Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels.

Molecular Mechanisms Regulating the Defects in Fragile X Syndrome Neurons Derived from Human Pluripotent Stem Cells

“…Our work lays a foundation for identifying a biomarker for early detection of the syndrome in affected embryos and suggests several candidates for targeted therapy. Recent studies suggest that REST plays a key role in the pathological process of different human neurodegenerative diseases ( González-Castañeda et al., 2013; Marullo et al., 2010; Zuccato et al., 2003 ). The role of REST in FXS should be furthered explored as well as the part that miRNAs play in the development of this pathology.…”

“…REST is expressed in embryonic stem cells (ESCs), NPCs, and nonneuronal cells, where it suppresses neuron-specific genes, in contrast to differentiated neurons where it is silenced ( Chen et al., 1998; Schoenherr and Anderson, 1995 ). REST both regulates and is regulated by brain specific miRNAs and has been implicated to be involved in pluripotency and neurodegenerative pathologies ( González-Castañeda et al., 2013; Gopalakrishnan, 2009; Hermanson, 2008; Marullo et al., 2010; Ooi and Wood, 2007; Zuccato et al., 2003 ).…”

The Transcription Repressor REST in Adult Neurons: Physiology, Pathology, and Diseases

“…In the first study, investigation of brains from patients and a specific transgenic mouse model revealed considerable increases in REST with concomitant decreases of choline acetyltransferase (the key enzyme of acetylcholine biosynthesis) in neurons in the area of the nucleus of Meynert and in fibers traveling to the frontal and motor cortices, and to hippocampal area CA1. In light of the REST dependence of choline acetyltransferase expression and the relevance of cholinergic neurons in the development of the disease, the increase in REST was hypothesized as a mechanism of the induction of the overexpression and accumulation of β-amyloid and other proteins involved in neuronal degeneration ( González-Castañeda et al, 2013 ; Orta-Salazar et al, 2014 ).…”

Activity Evaluation and Toxicological Profile of New Potential Metal Protein Attenuating Compounds in Biological Models of Alzheimer S Disease

“…On the other hand, the dopaminergic system and systems involving neuropeptides remain mostly unaffected. (Smiley et al, 1999;Dringenberg, 2000;Marien et al, 2004;González-Castañeda et al, 2013;Toneff et al, 2013).…”

“…methyl-D-aspartate receptor antagonists and medications for anxiety, depression, and psychosis (Ellul et al, 2007;Cunningham & Passmore, 2013;González-Castañeda et al, 2013). In some cases, the use of vitamin E in combination with other drugs is also prescribed (Barnes & Yaffe, 2005).…”