Current Alzheimer Research - Volume 9, Issue 5, 2012

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In recent years, in parallel with the growing awareness of the multifactorial nature of Late Onset Alzheimer's Disease, the possibility that epigenetic mechanisms could be involved in the onset and/or progression of the pathology assumed an increasingly intriguing and leading role in Alzheimer's research. Today, many scientific reports indicate the existence of an epigenetic drift during ageing, in particular in Alzheimer's subjects. Read More

Aberrations in epigenetic marks have been associated with aging of the brain while caloric restriction (CR) and upregulation of endogenous antioxidants have been suggested as tools to attenuate the aging process. We have recently observed age-related increases in levels of 5-methylcytidine (5-mC) and DNA methyltransferase 3a (Dnmt3a) in the mouse hippocampus. Most of those age-related changes in these Read More

Epigenetic modifications have been proposed to underlie age-related dysfunction and associated disorders. 5- hydroxymethylcytosine (5-hmC) is a newly described epigenetic modification. It is generated by the oxidation of 5- methylcytosine (5-mC) by the ten-eleven translocation (TET) family of enzymes. Various studies have shown that 5-hmC is present in high levels in the brain. Its lower affinity to methyl-binding proteins as co Read More

The vast majority of Alzheimer's disease (AD) are late-onset forms (LOAD) likely due to the contribution of genetic, environmental, and stochastic factors, superimposed on a physiologically age-related decline of neuronal functions. Increasing evidence indicates epigenetic modifications in LOAD brains, and many of the environmental factors associated with AD risk, such as heavy metals and dietary factors, are able to modi Read More

Late onset Alzheimer's disease (LOAD) is typical of the majority of Alzheimer's disease (AD) cases (∼90%), and has no clear genetic association. Previous studies from our lab suggest that an epigenetic component could be involved. Developmental exposure of primates and rodents to lead (Pb) predetermined the expression of AD-related genes, such as the amyloid-β precursor protein (AβPP), later in life. In addition to AβPP, Read More

Several lines of evidence indicate that the etiology of late-onset Alzheimer's disease (LOAD) is complex, with significant contributions from both genes and environmental factors. Recent research suggests the importance of epigenetic mechanisms in defining the relationship between environmental exposures and LOAD. In epidemiologic studies of adults, cumulative lifetime lead (Pb) exposure has been associated with Read More

Late onset Alzheimer's disease (LOAD) is a non-familial, progressive neurodegenerative disease and the most prominent form of dementia in the elderly. Accumulating evidence suggests that LOAD not only results from the combined effects of variation in a number of genes and environmental factors, but also from epigenetic abnormalities such as histone modifications or DNA methylation. In comparison to monogenic diseases Read More

Alzheimer's disease (AD) is a leading cause of aging related dementia and has been extensively studied by several groups around the world. A general consensus, based on neuropathology, genetics and cellular and animal models, is that the 4 kDa amyloid β protein (A&bgr) triggers a toxic cascade that induces microtubule–associated protein τ (MAPT) hyperphosphorylation and deposition. Together, these lesions lead to neu Read More

We previously designed novel peptides-containing galantamine analogues. These compounds we analyzed for their putative inhibitory effect towards acetylcholinesterase, butyrylcholinesterase and γ-secretase, three activities of which could be central to various neurodegenerative pathologies including Alzheimer's disease. These pharmacological agents were virtually equipotent on acetylcholinesterase activity but d Read More

Amyloid β protein (Aβ) is the primary component of senile plaques in Alzheimer's disease brains and its aggregate form is neurotoxic. Aβ is generated through proteolysis of β-amyloid precursor protein (APP) by two proteases: β-secretase and γ-secretase. BACE1, the β-secretase in vivo and the key rate-limiting enzyme that initiates the formation of Aβ, is an attractive drug target for AD therapy. Our previous study demo Read More

Due to an oversight the name of an author was published wrong in article entitled “Involvement of rat hippocampal astrocytes in β-amyloid-induced angiogenesis and neuroinflammation” in journal “Current Alzheimer Research, 2010, Vol. 7, no. 7. pp. 591-601.” The correct names of authors are given below: Fioravanzo L, Venturini M, Di Liddo R, Marchi F, Grandi C, Parnigotto PP, Folin M