Parkinson's Disease Symptoms, Pathology, Diagnosis And Treatment

Parkinson's disease(PD) is the second most common neurodegenerative disease.  It is caused by loss of dopaminergic neurons from substantia nigra. Loss of these neurons results in the deficiency of dopamine. Deficiency of Dopamine is responsible for the symptoms of PD. Symptoms of Parkinson's disease mostly appear in people greater than 50 years of age, but some cases symptoms can appear in adult age.

Main features of  Parkinson's disease are resting tremors, Bradykinesia, Rigidity. Secondary manifestations are defective posture and gait, Mask like face(masked facies), slurred speech, sleep disturbances, mood disorders. No cure is available for Parkinson's disease only treated by medications.

If the patient is not treated for long periods of time, then the symptoms get worse, patients become stiff, unable to move, unable to breath properly.

Etiology and Pathogenesis-


Etiology of most cases of Parkinson's disease is unknown. Some studies have described the role of genetic and environmental factors.


Role of α-synuclein

SNCA is the first known gene that is responsible for Parkinson's disease, which encodes α- synuclein protein. alpha-synuclein is present presynaptically in the neurons. Mutations in the SNCA gene is responsible for both sporadic and rare familial forms of Parkinson'ss disease.



  • α-synuclein is major constituents of Lewy bodies. Lewy bodies are a pathological hallmark of Parkinson's disease. Aggregates of Lewy bodies are present in the brainstem of PD patients. Lewy bodies show prion-like spread pattern in the brain.

Mitochondrial dysfunction-


  • Mutations in the gene that encodes the protein DJ-1, PINK-1 and Parkin causes mitochondrial dysfunction and responsible for autosomal recessive forms of PD.

  • Kinase PINK-1 is degraded under normal circumstances in mitochondria, but In the case of mitochondrial dysfunction, PINK-1 accumulate on the outer membrane of mitochondria and recruits Parkin protein which is an E3 ubiquitin ligase. This Parkin protein induces selective autophagy in mitochondria.


  • DJ-1 protein plays multiple roles, act as transcriptional regulators and protect mitochondria from oxidative stress.

  • Inhibition of complex-1 in mitochondria by toxin MPTP-1 causes a sporadic form of Parkinson's disease. It's created difficulty in the transport of electron in electron transport chain.

Role of LLRK-2 gene-

  • Mutations in the LLRK-2 gene- is responsible for autosomal dominant and sporadic forms of PD. Mutations in the LLRK-2 gene alter the kinase activity and phosphorylation of the substrate.

Differential Diagnosis-


Diagnosis of Parkinson is made on the basis of findings of neuroimaging, clinical symptoms and response to levodopa therapy.

Parkinson's disease should be differentiated from Parkinsonism, which shares the symptoms of Parkinson's disease (rigidity, bradykinesia, tremors and defective posture). 80% cases of parkinsonism are diagnosed as Parkinson's disease or idiopathic Parkinson disease.  Differential diagnosis of Parkinson include following-

(A) Atypical parkinsonism

  1. Progressive supranuclear palsy (PSP)
  2. Multiple system atrophy (MSA)
  3. Corticobasal degeneration
  4. Frontotemporal dementia


(B) Secondary parkinsonism

  1. Drug induces
  2. Tumor
  3. Infection
  4. Vascular
  5. Trauma
  6. Toxins(MPTP)
(C) Other neurodegenerative diseases
  1. Wilson's disease
  2. Huntington's disease
  3. Dystonia-Parkinsonism
  4. Prion disease

Treatment-

(A) Treatment by drugs

  1. Levodopa- Levodopa is administrated in combination with peripheral carboxylase inhibitor. peripheral carboxy inhibitor is used to prevent its peripheral metabolism to dopamine.
  2. COMT inhibitors- Tolcapone and Entacapone are COMT inhibitors used in the treatment of PD.
  3. Dopamine agonists- E.g.- Bromocriptine and pergolide.
  4. MAO-B inhibitors- E.g.- selegiline and rasagiline.
  5. Centrally acting anticholinergics- Trihexyphenidyl and Benztropine.

(B) Surgical treatment

Deep brain stimulation(DBS) is used to treat symptoms of  PD. In this procedure, an electrode is placed into the target area and impulses produced by stimulator are sent to targeted area through electrode.

(C) Nonpharmacological therapy

physical exercise with a wide range of active movements improve symptoms of PD in some patients and also reduces the risk of arthritis and frozen joints.

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