Home / Summaries / Het zenuwstelsel / pd-ab-parkinsons

Neurodegeneratieve ziektes

15 important questions on Neurodegeneratieve ziektes

Parkinsons disease symptoms

–Hypokinetic disorder (reduced motor activity)
–Tremor (4-7 Hz) of the limbs
–Increased muscle tone
–Muscle rigidity
–Difficulty in initiating movements (akinesia)
–Slow movements (bradykinesia)
–Mask-like facial expression
–Low eye blink rate
–Bend back during walking
–Shuffling gait

Parkinsons disease etiology (two variants)

•Familial PD is rare
–Mutations in the gene encoding a synuclein
–Presence of Lewy bodies
•Sporadic PD
–Head trauma
–Brain tumors
–Environmental toxins, -MPTP (MPTP is een organische verbinding die toxische effecten heeft op de substantia nigra, een gebied in de hersenen dat onder andere de motoriek regelt. MPTP zorgt ervoor dat cellen afsterven, waardoor het gebied zijn functie niet meer kan uitoefenen)

Parkinsons disease: neuropathology

–Loss of dopamine neurons in the substantia nigra pars compacta (SNpc; nigrostriatal pathway)
•A 50% loss of SNpc neurons is necessary for onset of symptoms, SNpc neurons die from oxidative stress
–Other dopamine neurons, noradrenergic neurons and cholinergic neurons also die, but to a lesser extent

So: Normally, misfolded proteins are degraded, in PD, mutated synuclien accumulates in Lewy bodies, this causes oxidative stress and neurodegeneration

How do SNpc neurons die from oxidative stress in Parkinsons disease?

oxidative stress plays a central role in the degeneration and death of SNpc neurons in Parkinson's disease by causing mitochondrial dysfunction, oxidative damage, protein aggregation, and activation of cell death pathways.
–DA metabolism enhances oxygen radical formation
–Neuromelanin binds Fe++ and promotes hydroxyl radical formation

Lewy bodies in Parkinsons Disease

The histological hallmark of Parkinson's disease (PD) is the presence of fibrillar aggregates called Lewy bodies (LBs). LB formation has been considered to be a marker for neuronal degeneration, because neuronal loss is found in the predilection sites for LBs.
Composition:
Cytoplasmic inclusions with a core of a-synuclein (protein that is mutated in PD) and a halo of ubiquitin (small protein that is coupled to other proteins and marks these proteins for degradation )

Braak stages of Parkinson disease

1. Brain stem & olfactory system
2. Laesies medulla oblongata
3. Substantia nigra (more and more accumulating lewy bodies)
4. Ernstige beschadiging doparmergic neurons
5. Neocortex and lobes
6. Whole neocortex, bad movement and perception

Earliest affected brain areas in PD?

–The earliest affected brain structures in PD are the dorsal nuclei in the brain stem and the olfactory bulb

Pharmacological treatment PD (4)

•L-DOPA (+ DOPA decarboxylase inhibitor)
–Increases dopamine synthesis
•MAO inhibitors
–Prevents breakdown of dopamine
•Antioxidants (vitamin E)
–Bind free oxygen radical
•Dopamine receptor agonists
–Stimulate dopamine receptors on striatal neurons

Surgical treatment PD (3)

•Lesions
-Lesioning specific output regions of the striatum reduce PD symptoms in animals and humans
•Cell or tissue transplantation
-Transplantation of fetal SNpc tissue or neurons results in partial improvement (Ethical concerns, alternative sources for dopamine neurons (stem cells))
•Deep Brain Stimulation
-involves implanting electrodes into specific areas of the brain and delivering electrical impulses to modulate abnormal neuronal activity.

Deep Brain Stimulation Parkinsons Disease

During the electrode placement surgery, the neurosurgeon implants thin, insulated electrodes into specific targets within the brain, typically the subthalamic nucleus (STN) or the globus pallidus internus (GPi). The electrodes are connected by extension wires that are tunneled under the skin to a pulse generator device, which is implanted in the chest or abdominal wall during a separate surgical procedure.

Alzheimers Disease: prevalence & symptoms

•Prevalence and symptoms:
–Commonest cause of dementia in the elderly (Affects 5% of people over 70 and 20% of people over 80)
–Causes serious cognitive impairment
•Loss of memory
•Decreased attention and motivation
–Progression is uneven in different individuals (Stress can accelerate progression)
–Most AD patients also have PD and suffer from depression
–Life expectancy after diagnosis is ~5 years

Neuritic plaques and neurofibrillary tangles in AD

•Neuritic plaques
–Extracellular lesions containing an insoluble form of the peptide b-amyloid (Ab)
•Neurofibrillary tangles
–Cytoplasmic bundles of hyper-phosphorylated tau proteins

Alpha beta gamma secretases AD

Alpha-secretase: Cleaves amyloid precursor protein (APP) within its transmembrane domain, preventing the formation of amyloid-beta (Aβ) peptides.

Abnormal:

Beta-secretase (BACE): Cleaves APP at the N-terminus of the Aβ peptide sequence, leading to the production of Aβ peptides, which aggregate to form amyloid plaques in Alzheimer's disease.
Gamma-secretase: Cleaves the C99 fragment generated by beta-secretase, releasing the Aβ peptide.

AD: why is beta-amyloid toxic? (3)

Normal role of Ab is poorly understood (Ab binds Cu++ and may act as an antioxidant). Overproduction of Ab is a necessary condition for AD.
Toxic:
–When Ab binds Cu++ it produces H2O2 and causes oxidative stress
–Small Ab aggregates cause damage to axons and synapses
–Ab-derived diffusible ligands (ADDLs) may specifically impair synaptic function (inhibit LTP) and cause neuronal apoptosis

Pharmacological treatment AD (7, not all succesful)

-Acetylcholinesterase inhibitors (neostygmine, donezepil): Improves cholinergic functions (memory consolidation). Not very successful.
-Anti-inflammatory drugs (indomethacin): Targets inflammatory components of AD.
-Vaccination against Ab: Not successful. Causes brain inflammation.
-Chelating agents (clioquinol): Binds Cu++ and Zn++.
-Antioxidants: Bind free oxygen radicals.
-Neurotrophins: Proteins that promote neuronal survival and growth.
-Inhibitors of b- and g-secretase

The question on the page originate from the summary of the following study material:

Het zenuwstelsel

View summary

A unique study and practice tool
Never study anything twice again
Get the grades you hope for
100% sure, 100% understanding

Remember faster, study better. Scientifically proven.

Neurodegeneratieve ziektes

15 important questions on Neurodegeneratieve ziektes

Parkinsons disease symptoms

Parkinsons disease etiology (two variants)

Parkinsons disease: neuropathology

How do SNpc neurons die from oxidative stress in Parkinsons disease?

Lewy bodies in Parkinsons Disease

Braak stages of Parkinson disease

Earliest affected brain areas in PD?

Pharmacological treatment PD (4)

Surgical treatment PD (3)

Deep Brain Stimulation Parkinsons Disease

Alzheimers Disease: prevalence & symptoms

Neuritic plaques and neurofibrillary tangles in AD

Alpha beta gamma secretases AD

AD: why is beta-amyloid toxic? (3)

Pharmacological treatment AD (7, not all succesful)

Summaries related to Neuronale ontwikkeling

Het zenuwstelsel

Indian Economics

Global politics

Essentials of international relations

Behavioral genetics

Management and organisational behaviour

Follow Up Engels idioom 4/5 H

International Business

Marketing fundamentals

Projectmanagement, A practical Approach-Engl…

Basic Management Accounting for the Hospital…

International business