Etiology of parkinsons

Question 1

What was the first gene code for that was discovered in Familial parkinson?

Answer 1

Coded for synuclein

occurs in 10% of PD patients

Question 2

What is the pathogenesis of PD?

Answer 2

1. Mitochondrial dysfunction.
   2. Impaired degradation of intracellular proteins (i.e., Ubiquitin-proteosomal system) or organelles (i.e.,
      Autophagy).
   3. Impaired transport of organelles (e.g., mitochondria) and proteins (microtubule dynamics).
   4. Disruption of synaptic homeostasis (i.e., abnormal accumulation of synuclein —- Lewy bodies).

Question 3

What is the etiology of sporadic parkinson?

Answer 3

Sporadic PD (>90%): no significant gene association, but associated with several RISK FACTORS:

Question 4

What are the risk factors of sporadic PD?

Answer 4

Infections (e.g., encephalitis): Epidemic

Trauma: Head injury (e.g., boxers; Ali)

Endocrine: (e.g., hypothyroidism),

Wilson’s disease — altered Cu2+ metabolism

Drugs (various types) or Toxins

Question 5

What are the drugs are risk factors for sporadic PD?

Answer 5

Neuroleptics: e.g., haloperidol (D2 antagonist)
Metoclopramide: D2 receptor antagonist
Reserpine — Depletes nerve terminal DA, NE
Pesticides: Mitochondrial dysfunction
MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) – Neurotoxin; meperidine analog. 1-MPP+ —- toxic metabolite

Question 6

What are the cardinal clinical symptoms (motor symptoms) features of PD?

Answer 6

Mnemonic TRAP 
Tremor at rest
   - Earliest symptom in 75% PD.
    - ‘Pill-rolling’ (3-5 Hz/sec) 
 Rigidity (cogwheel) 
 Akinesia/bradykinesia
 Postural reflex impairment (falls)

Question 7

What are early Non motor symptoms of parkinson Disessae?

Answer 7

Sleep abnormalities (
Autonomic dysfunction (constipation)
sensory (olfactory dysfunction)
Fatigue and weight loss

Question 8

What is the Functional Neuroanatomy of PD?

Answer 8

Progressive and selective degeneration of dopaminergic (DA) neurons in the substantia nigra (pars compacta) within the basal ganglia leads to a reduction of DA in the striatum.

Question 9

What is the nigrostriatal pathway a part of?

Answer 9

The Nigrostriatal Pathway is part of the extrapyramidal system (EPS) that regulates fine motor movement, muscle tone and posture

EPS modifies the output of descending motor pathways to turn gross uncoordinated movement into finely coordinated movements.

Question 10

How does the Nigrostriatal pathway modulate fine motor control?

Answer 10

• The nigrostriatal pathway modulates the direct and indirect pathways by exciting one pathway (DIRECT) while simultaneously inhibiting the other (INDIRECT).

Question 11

What is the direct pathway in the Nigrostrial pathway?

Answer 11

Direct pathway striatal neurons have D1 dopamine receptors, which DEPOLARIZE the cell in response to dopamine

Question 12

What is the indirect pathway in the nigrostrial pathway?

Answer 12

• Indirect pathway striatal neurons have D2 dopamine receptors, which HYPERPOLARIZE the cell in response to dopamine.

Question 13

How is the direct and indirect pathway modified in PD its?

Answer 13

• The loss of DA neurons in PD causes the poverty of movement by altering the balance between the direct pathway excitation of cortex and indirect pathway inhibition of cortex. This causes a tipping in favor of the INDIRECT PATHWAY, with a subsequent pathological global inhibition of motor cortex areas (i.e., fine motor function).