http://www.faculty.umb.edu/pjt/epi/jick00.pdf

Statins and the risk of dementia.

Oxidative stress in Alzheimer's disease brain: New insights from redox proteomics

Functions and dysfunctions of nitric oxide in brain.

The aim of this review is to summarise the recent findings in the fields of carcinogenesis and neurodegenerative diseases, the both disorders are characterised by the contribution of different factors including the inheritance of mutated genes, and the exposure to endogenous or exogenous agents during the life. We first analysed the causative genes until now discovered in both processes, then we focused our attention on the role of environmental exposure, susceptibility factors, oxidative stress, apoptosis and aging to the development of such disorders. The genotype at a particular locus may account for an inter-individual susceptibility that can both increase or decrease the risk to develop the pathology especially after the exposure to environmental agents. The mechanism of apoptosis, that is an excellent strategy in order to eliminate damaged cells, seems to be lost during carcinogenesis, while it seems to be involved in the neuronal death in a lot of neurodegenerative disorders. Oxidative stress can both lead to DNA mutations or to the formation of damaged proteins, so being an important risk factor for the initiation and the progression of a disease: in fact it may be one of the causes or can arise as a consequence of a damage caused by other factors increasing then the first damage. It is well established that carcinogenesis is a multi-step process caused by series of successive mutations occurring into a cell and conferring to this cell a growth advantage, so that age is the largest risk factor for cancer in humans. Pathophysiology of neurodegenerative diseases is complex and likely involves multiple overlapping and perhaps redundant pathways of neuronal damage, characterised by the generation of anomalous proteins, often due to mutations in the corresponding gene, and by their subsequent accumulation into or outside specific areas of the brain.

Genetic and environmental factors in cancer and neurodegenerative diseases.

Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues.

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder of later life. Genetic studies have demonstrated that the apolipoprotein E (ApoE) gene is an important susceptibility locus; however, other environmental and genetic factors operating alone or in combination with ApoE must also be involved. Among candidate genes that may contribute to this residual risk is the endothelial nitric oxide synthase (NOS3) gene. NO release from vascular endothelium accounts in large part for endothelium-derived relaxing factor bioactivity. Abnormalities of cerebral small vessels occur early in AD, and it has been demonstrated recently that beta-amyloid interacts with endothelial cells in blood vessels to produce an excess of superoxide radicals. We have genotyped 122 cases of early-onset AD (EOAD) and 317 cases of late-onset AD (LOAD) as well as 392 controls for a common structural polymorphism Glu/Asp at codon 298 in the NOS3 gene. We find a highly significant enrichment for Glu/Glu homozygotes in LOAD compared with controls. The effect appears to be independent of ApoE status. NOS3 may be a new genetic risk factor for LOAD.

Association between Alzheimer's disease and the NOS3 gene.

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Association between Alzheimer's disease and the NOS3 gene.