Scribd
Upload
27 views13 pages

Cell Cycle Markers in Huntington's Disease

This document discusses the effect of cell cycle marker re-expression in aged neurons in Huntington's disease pathogenesis. Huntington's disease is caused by a mutation in the HTT gene and causes progressive neuronal breakdown. It can be aggravated by re-entry of neurons into the cell cycle, driven by factors like reactive oxygen species, altered CDK5 activity, and the neurotoxin 3-nitroproprionic acid. MicroRNA-124 helps control this process and regulates pro-survival signals. Re-expression of cell cycle markers like cyclins can lead neurons to improperly re-enter the cell cycle, undermining neuronal homeostasis.

Uploaded by

Winrad D. Velarde
Copyright
© All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
27 views13 pages

Cell Cycle Markers in Huntington's Disease

This document discusses the effect of cell cycle marker re-expression in aged neurons in Huntington's disease pathogenesis. Huntington's disease is caused by a mutation in the HTT gene and causes progressive neuronal breakdown. It can be aggravated by re-entry of neurons into the cell cycle, driven by factors like reactive oxygen species, altered CDK5 activity, and the neurotoxin 3-nitroproprionic acid. MicroRNA-124 helps control this process and regulates pro-survival signals. Re-expression of cell cycle markers like cyclins can lead neurons to improperly re-enter the cell cycle, undermining neuronal homeostasis.

Uploaded by

Winrad D. Velarde
Copyright
© All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd

MBB 201 l 1st SEM AY 2017-2018 l CELL

CYCLE

The effect of cell cycle markers re-expression


in aged neurons in the pathogenesis of
Huntingtons Disease

Presented by:
Nicci Rosietess E. Madarcos, MS BOT
Cell cycle markers MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
(Cyclins, CDKs, B/cdk1
Cdc25
CDKIs)
C/cdk3

p53

p15Ink4b
p16Ink4a
A/cdk1 p18Ink4c
Cell Cycle A/cdk2
p21Cip1
D/cdk4/6 p19Ink4d
p27Kip1
Homeostasis p57Kip2
E/cdk2
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
HUNTINGTONS DISEASE
Huntingtons disease (HD) is a dominantly
inherited disorder that causes the progressive
breakdown of nerve cells in the brain.

mutation (high number in CAG


repeats) in the huntingtin (HTT) gene
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
HUNTINGTONS DISEASE

It deteriorates a persons physical and mental


abilities during their prime working years and
has no cure.

It can be further aggravated by re-expression


of cell cycle markers in aged neurons
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE

HUNTINGTONS DISEASE
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
Reactive Oxygen Species (ROS)
DNA Damage and Calpain activation by
hydrogen peroxide (H2O2-) repair Ca2+

p53 CDK 5

Growth factors p27

Cyclin D
Cyclins
superoxide anion (O2.-)
hydroxyl radical (.OH)
Cell cycle re entry
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
Altered Cdk5 Activity

p27

Cell cycle re entry


MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE

Neurotoxin: 3-nitroproprionic acid (3NP)


Present in plants Calpain activation by Ca2+
(Astragalus) and fungi CDK5/p25 pathway
(Anthrinium)

D/Cdk4 P
E/Cdk2 Rb protein

p27

Cell cycle re entry


MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE

miRNA-124: Brain specific microRNA


crucial regulators for
neural differentiation in
neurodegeneration Cyclin A

controls neural survival by


regulating pro-survival and
pro-apoptotic signals

regulate proliferation of
neural progenitor cells
Cell cycle re entry
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE

References:
Das, E., Jana, NR., Bhattacharyya, NP. (2013). MicroRNA-124 targets CCNA2 and
regulates cell cycle in STHdh(Q111)/Hdh(Q111) cells. Biochem Biophys Res Commun
437:217-224. DOI: [Link]

Folch, J., Junyent, F., Verdaguer, E., Auladell, C., Pizarro, J., Beas-Zarate, C., Pallas, M., and
Camins, A. (2012). Review: Role of Cell Cycle Re-entry in Neurons: A Common Apoptotic
Mechanism of Neural Cell Death. Neurotox Res 22: 195-207. DOI: 10.1007/s12640-011-
9277-4.

Sharma, R., Kumar, D., Jha, N., Jha, S., Ambasta, R., and Kumar, P. (2016). Invited Review:
Re-expression of cell cycle markers in aged neurons and muscles: Whether cells should
divide or die. Molecular Basis of Disease. doi: 10.1016/[Link].2016.09.010.
MBB 201 l 1st SEM AY 2017-2018 l CELL
CYCLE

THANK
YOU!!

You might also like