neurology-2018-posters-abstracts

t h

E u r o S c i C o n C o n f e r e n c e o n

Neurology & Neurological

Disorders

Neurology 2018

J u l y 1 2 - 1 3 , 2 0 1 8

P a r i s , F r a n c e

Page 96

Journal of Neurology and Neuroscience

ISSN: 2171-6625

strocytic activation initiating neuroinflammation is closely associated with many neurodegenerative diseases including

Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Multiple Sclerosis (MS). Neuronal

insults lead to deregulation and hyperactivation of Cdk5, the major neuronal cell cycle kinase, in the nervous system initiates

neuropathology. Using p25Tg AD model mice (CaMPKII P25Tg) we found that initially astrocytes are activated due to higher

activity of phospholipase 2A (PLA2) induced by Cdk5 phosphorylation of Cdk5 consensus sequence in PLA2 and affecting

phospholipid metabolism. This leads to increase in factors like arachidonic acid and activation of neuroinflammation and

neurodegeneration. It is well known that under physiological conditions, the initial interactions among neurons, astrocytes,

microglia, and oligodendrocytes are regulated and induce secretion of basal levels of various factors e.g. complement proteins,

cytokines and chemokines essential for physiological conditions. The expression of these diverse molecules is tightly regulated

since they act as trophic factors essential for nervous system development and function. However, under stress and toxic

conditions, additive effects of neuronal chronic stress/insults/toxicity, in addition to ageing leads to overexpression of these

factors which leads to neuroinflammation and neurodegeneration. A systematic, time course study of the expression and

activation of these factors provided the evidence that activation of astrocytes is the initial step in the deregulation of Alzheimer’s

disease in AD model system.

Initial activation of astrocytes / deregulation of

Cdk5 Axis in AD and Alzheimer’s diseases

Harish C Pant

NIH / NINDS, Bethesda, Maryland

J Neurol Neurosci 2018, Volume: 9

DOI: 10.21767/2171-6625-C1-009