"Genetic Etiology of Parkinson Disease" Presentation. Master of Molecular Genetics, Semester 3.

1. Genetic Etiology of Parkinson Disease
Parisa Sadat Naji Esfahani
Dr. Khatami
Summer 2018

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3. Clinical Features of Parkinson Disease
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Pathways on Parkinson Disease
i. Synaptic Transmission or Dopamine Signaling
SNCA
ii. Mitochondrial Quality Control or mitochondrial damage repair pathway
DJ1, PINK1, PRKN
iii. Lysosome – Mediated Autophagy or MAPKKK Signaling
LRRK2

6. Major Genes and Proteins in Parkinson Disease
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7. SNCA at 4q21
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• PARK1 & 4 or α-synuclein of Synuclein Family
• 140 amino acid
• AD Gene
• Roles:
1. Integrate Presynaptic Signaling & Membrane
Trafficking
2. Regulate the Release of Dopamine
3. Microtubules Movements

8. LRRK2 at 12q12
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• PARK8 or Leucine_rich repeat kinase 2 or Dardarin
• 2527 amino acid
• AD Gene
• Roles:
1. SNCA Phosphorylation
2. Microtubule Dynamics
3. Immune System Cells
4. Autophagic Alterations
5. Synthesis & Trafficking of Vesicles
6. Mitochondrial Function
7. UPS Alterations

9. PRKN at 6q26
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• PARK2 or Parkin
• 456 amino acid
• AR Gene
• Roles:
1. E3 Ubiquitin Ligases
2. Trigger the Destruction of Mitochondria
3. Tumor Suppressor Protein
4. Release Synaptic Vesicles from Nerve
Cells

10. PINK1 at 1p36.12
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• PARK6 or PTEN-induced putative kinase 1
• 581 amino acid
• AR Gene
• Roles:
1. Mitochondrial Dysfunction

11. DJ1 at 1p36.23
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• PARK7
• Oncogene
• AR Gene
• Roles:
1. A Positive Regulator of Androgen
Receptor-dependent Transcription
2. Redox-sensitive Chaperone (as a Sensor
for Oxidative Stress)
3. Protects Neurons against Oxidative Stress
& Cell Death

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13. Mutation of Parkinson Disease
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15. Mode of Inheritance in Parkinson Disease
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16. Mode of Inheritance in Parkinson‘s Disease
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Sporadic or Familial?

18. Risk Factors
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19. Progression of Parkinson’s disease pathology
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20. Progression of Parkinson’s disease pathology
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21. New Informations about Parkinson‘s Disease
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Elements concentration in CSF and serum of PD versus control

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