Parkinson Disease

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1- Introduction

2- Pathophysiology

3- Causes

4- Treatment 

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that primarily affects movement. It results from the loss of dopamine-producing neurons in the substantia nigra, a region of the brain that plays a crucial role in movement control.
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Pathophysiology

  • Dopaminergic Neuron Degeneration:

    • Loss of dopaminergic neurons in the substantia nigra pars compacta leads to a decrease in dopamine levels in the striatum.

  • Lewy Bodies:

    • Abnormal aggregates of protein, primarily alpha-synuclein, found within neurons, are a hallmark of Parkinson’s disease.

  • Basal Ganglia Dysfunction:

    • The basal ganglia, which are involved in regulating movement, become dysfunctional due to the dopamine deficiency.

Causes

  • The exact cause of Parkinson’s disease (PD) remains unknown, but it is believed to result from a combination of genetic, environmental, and possibly other factors.

  • Genetic Factors

    1. Genetic Mutations:

      • SNCA (Alpha-Synuclein): Mutations in this gene can lead to the production of abnormal alpha-synuclein, a protein that forms Lewy bodies.
      • LRRK2 (Leucine-Rich Repeat Kinase 2): The most common genetic cause of PD, particularly in certain populations.
      • PARK2 (Parkin): Associated with early-onset Parkinson’s disease.
      • PINK1 (PTEN-Induced Putative Kinase 1) and DJ-1: Other genes linked to familial forms of PD.

    2. Inheritance Patterns:

      • While most cases of PD are sporadic, a small percentage (around 10-15%) are familial, meaning they run in families due to inherited genetic mutations.

    Environmental Factors

    1. Toxins and Chemicals:

      • Pesticides and Herbicides: Exposure to substances like paraquat and rotenone has been linked to an increased risk of developing PD.
      • Industrial Chemicals: Solvents such as trichloroethylene (TCE) and polychlorinated biphenyls (PCBs) have been implicated.

    2. Heavy Metals:

      • Exposure to heavy metals like manganese and lead may contribute to the development of Parkinson’s disease.

    3. Rural Living:

      • Higher prevalence in rural areas possibly due to increased exposure to agricultural chemicals.

    Other Potential Factors

    1. Age:

      • Aging is the most significant risk factor. The risk of developing PD increases with age, typically affecting individuals over the age of 60.

    2. Oxidative Stress:

      • Imbalance between free radicals and antioxidants in the body can lead to neuronal damage.

    3. Mitochondrial Dysfunction:

      • Mitochondria, the energy-producing components of cells, may not function properly, leading to neuron damage.

    4. Inflammation:

      • Chronic inflammation in the brain might contribute to neurodegeneration.

    5. Head Injury:

      • A history of severe head trauma may increase the risk of PD.

    6. Viral Infections:

      • Certain viral infections have been hypothesized to trigger PD, though conclusive evidence is lacking.

Treatment

  • Medications:

    1. Levodopa:

      • The most effective treatment, often combined with carbidopa to prevent peripheral breakdown.

    2. Dopamine Agonists:

      • Drugs like pramipexole, ropinirole, and rotigotine mimic dopamine effects.

    3. MAO-B Inhibitors:

      • Selegiline and rasagiline inhibit the breakdown of dopamine.

    4. COMT Inhibitors:

      • Entacapone and tolcapone prolong the effect of levodopa.

    5. Anticholinergics:

      • Used to treat tremors, such as benztropine and trihexyphenidyl.

    6. Amantadine:

      • Can help with dyskinesia and mild symptoms.

    Non-Pharmacological Treatments:

    1. Physical Therapy:

      • Exercises to improve mobility, flexibility, and balance.

    2. Occupational Therapy:

      • Techniques to assist with daily activities.

    3. Speech Therapy:

      • Helps with speech and swallowing difficulties.

    Surgical Treatments:

    Deep Brain Stimulation (DBS):
    • Electrodes implanted in the brain deliver electrical impulses to modulate abnormal activity.
    • Effective for patients who do not respond well to medications.
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