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Journal of Neurology and Neurorehabilitation Research
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Volume 3
Page 24
Note:
allied
academies
J u n e 2 8 - 2 9 , 2 0 1 8 | D u b l i n , I r e l a n d
Joint Event on
NEUROSCIENCE AND NEUROLOGICAL DISORDERS
PSYCHIATRY AND PSYCHOLOGICAL DISORDERS
&
International Conference on
International Conference on
NEUROPROTECTIVE ROLE OF A SMALL
PEPTIDE DERIVED FROM NEURONAL
CELL CYCLE LIKE KINASE (CDK5)
ACTIVATOR (P35)
Harish C Pant
National Institutes of Health, USA
C
dk5 is a member of cyclin-dependent kinases. It is unique among Cdk
family of kinases; it is not activated by cyclins but is activated exclusively
by the brain-specific p35/p25 proteins. It is a multifunctional protein kinase
constitutively active in nervous tissues. It is implicated in ameliorating various
neurodegenerative diseases phenotypes including AD. Cdk5, (Cdk5/p35),
activity is tightly regulated and essential for nervous systemdevelopment and
neuronal functions. Emerging evidence suggests that its deregulation and
hyper activation due to neuronal insults produced p25 and accumulation and
aggregation of synaptic and cytoskeletal proteins in neuronal cells forming
early stages of neurofibrillary tangles, plaques, Lewy bodies inclusions.
These aggregated proteins and peptides are the hallmarks of AD, PD and ALS
pathologies. On the basis of a large number of studies we have proposed
Cdk5/p35 is a physiological and Cdk5/p25 is pathological target. To reduce
the pathological phenotypes
in situ
/
in vivo
we discovered p5, a 24-amino
acid truncated peptide from Cdk5 activator protein, p35, selectively inhibited
the deregulated and hyperactive active Cdk5, (Cdk5/p25), induces pathology,
but not Cdk5, (Cdk5/p35), kinase essential for nervous system development,
function and survival. Recently it has been provided sufficient information
that a modified truncated 24-amino acid peptide (TFP5), derived from the
Cdk5 activator p35, penetrates the blood-brain barrier upon intraperitoneal
injections (ip), inhibits significantly abnormal Cdk5 hyperactivity, and rescues
significantly, AD pathology (up to 70–80%) in 5XFAD, p25Tg AD model. In
addition, MPTP induced phenotypes in Parkinson’s disease model mice. The
present talk will provide the molecular and cellular basis of the selectivity
of these two forms of kinases, Cdk5/p35 and Cdk5/p25, physiological and
pathological behavior of Cdk5/p35 and Cdk5/p25 kinases. We propose, TFP5
may be able to ameliorate several phenotypes in different neurodegenerative
disease.
Harish C Pant has received his MA and PhD
degrees in Physics from Agra University, Agra,
India. His postdoctoral studies were conducted
on the mechanisms of electron and ion trans-
port in model membrane systems at the Depart-
ment of Biophysics at Michigan State Universi-
ty. He joined the Laboratory of Neurobiology in
the NIMH as a Senior Staff Fellow in 1974 with
Ichiji Tasaki where he studied the function of
the axonal cytoskeleton in the squid giant axon.
In 1979, he moved to the NIAAA extending his
studies on the neuronal cytoskeleton and the
effects of alcohol on its regulation. He moved
to the NINDS, Laboratory of Neurochemistry in
1987, where he is presently Chief of the section
on cytoskeleton regulation. His laboratory is
studying the mechanisms of topographic reg-
ulation of neuronal cytoskeleton proteins by
post-translational modification, including the
role of kinase cascades in normal brain and
during neurodegeneration.
panth@ninds.nih.govBIOGRAPHY
Harish C Pant, J Neurol Neurorehabil Res 2018, Volume 3