MALADIE DE PARKINSON : APPORTS DE LA GENETIQUE

ETIOLOGY OF PARKINSON'S DISEASE environment toxins proteasome dysfunction genetic susceptibility factors inflammation monogenic forms oxidative.
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MALADIE DE PARKINSON : APPORTS DE LA GENETIQUE

Alexis BRICE Cricm, Inserm UMR_S975/CRNS UMR 7225/UPMC (PitiéSalpêtrière Hospital, Paris, France)

Parkinson’s disease

• Prevalence: 200 per 100,000

Age

< 40

> 60

>85

%

Rare

1

4

• Incidence: 20 per 100,000 annually • Male > female

Parkinson’s disease Neurodegenerative disease characterized by: ƒ Bradykinesia ƒ Rigidity ƒ Rest tremor ƒ Good initial reactivity to levodopa ƒ Selective degeneration of the nigrostriatal

dopaminergic pathway

ƒ Lewy bodies

PROGRESSION OF PARKINSON'S DISEASE

SN neurons (%)

100

Symptom onset

50

0 30

40

50

Age (years)

60

70

From Schulzer et al. Brain 1994;117:509-516

ETIOLOGY OF PARKINSON’S DISEASE

monogenic forms

proteasome dysfunction

environment toxins

oxidative stress increased iron mitochondrial dysfunction

genetic susceptibility factors

inflammation

FROM MONOGENIC TO MULTIFACTORIAL DISORDERS : A CONTINUUM? Monogenism G4

Digenism

G1

G3 Phenotype G2

G1

G5 G6 G7

G4

Multifactorial

G5

Phenotype

G3

G6

G3 G7

G2

Environment

Environment

Modifier genes

Modifier genes

G2 G1

G4 G5 G6

Phenotype

G7

Environment

Genetic susceptibility factors

PARKINSON’S DISEASE AND GENETIC FACTORS

Monogenic forms

Sporadic forms