Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.
Alzheimer�s disease (AD) is neuropathologically characterized by senile plaques made of Aβ 1-42 peptide, neurofibrillary
tangles composed by hyperphosphorylated tau protein and synaptic and neuronal losses. Aβ 1-42 is known to induce
neuronal death. PKR is a pro-apoptotic kinase that can phosphorylate the initiation factor eIF2α and reduce protein translation.
The activation of PKR is induced by virus, cytokines, calcium, and Aβ 1-42. PKR can also modulate inflammation and the
genetic knock down of PKR improves memory in experimental mice. Author�s group has been working on PKR for the last
years and we have shown that activated PKR accumulates in the degenerating neurons of AD patients and that PKR can
experimentally control the expression of the APP cleaving enzyme BACE1, reduce the production of Aβ peptide and indirectly
induce in neuronal cell cultures the phosphorylation of tau protein. In a recent study we have analyzed CSF levels of PKR
and activated PKR (pPKR) in AD patients compared to neurological controls and patients with amnestic Mild Cognitive
Impairment (MCI). The CSF of 45 AD patients, 11 patients with Mild Cognitive Impairment and 35 neurological controls
were assessed and the patients were followed for more than 2 years. CSF levels of Aβ 1-42, Tau, pTau, PKR and pPKR were
evaluated. Cognitive assessments were carried out twice a year. All patients or care givers gave their written inform consents.
The mean CSF pPKR level was increased (300%) in AD patients compared to neurological disease controls. The sensitivity was
91.1% and the specificity was 94.3%. Many MCI patients had also increased pPKR concentrations. In AD patients PKR and
pPKR levels correlate with pTau levels and with the cognitive decline assessed by MMSE over more than 2 years. In conclusion,
experimental and clinical data suggests that pPKR is detrimental to the formation of memory and that this activated kinase
interferes with the abnormal molecular pathways and the clinical evolution of the disease. PKR represents a possible new
biomarker and pharmacological target in AD.
Biography
Jacques Hugon Professor MD PhD Neurologist at Lariboisiere Hospital Centre Memoir (CMRR) at University of Paris. Chair, Professor, Head of the Department
at University of Hong Kong. A team from Lariboisiere Hospital, led by Pr Hugon in Paris France has just revealed that a potent killer enzyme, PKR, was activated
in the brain and cerebrospinal fluid (CSF) of AD patients. This team has found that the level of activated PKR was three time higher in the CSF of AD patients as
compared to controls. New researches are underway to attenuate its functions by new specific �kinase inhibitors� that could represent a powerful way to attenuate
memory deficits in AD patients.
Relevant Topics
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals