کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2589709 1562055 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb)
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb)
چکیده انگلیسی


• Developmental exposure to the lead (Pb) early in life affects the expression of the tau gene later in life.
• Pb increases the kinase activity of cdk5 and its p25 activator thus promoting the phosphorylation of tau and its pathogenicity.
• Early development is an important period of vulnerability, which could increase future susceptibility to taupathy.

Late Onset Alzheimer Disease (LOAD) constitutes the majority of AD cases (∼90%). Amyloidosis and tau pathology, which are present in AD brains, appear to be sporadic in nature. We have previously shown that infantile lead (Pb) exposure is associated with a change in the expression and regulation of the amyloid precursor protein (APP) and its beta amyloid (Aβ) products in old age. Here we report that infantile Pb exposure elevated the mRNA and protein levels of tau as well as its transcriptional regulators namely specificity protein 1 and 3 (Sp1 and Sp3) in aged primates. These changes were also accompanied by an enhancement in site-specific tau phosphorylation as well as an increase in the mRNA and protein levels of cyclin dependent kinase 5 (cdk5). There was also a change in the protein ratio of p35/p25 with more Serine/Threonine phosphatase activity present in aged primates exposed to Pb as infants. These molecular alterations favored abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates with prior Pb exposure. These findings provide more evidence that neurodegenerative diseases may be products of environmental influences that occur during the development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 39, December 2013, Pages 95–101
نویسندگان
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