Parkinsons Disease - Neurobiology and Aetiology

This slide deck covers the neurobiology and aetiology of Parkinson’s Disease (PD). Pathogenetic details, including underlying common pathways and treatment designs based on the pathogenesis model, are discussed. In addition, α-synuclein and the prion hypothesis of PD are briefly reviewed.

This slide deck has been developed in collaboration with the former Lundbeck International Neuroscience Foundation.

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Neurobiology and aetiology

This presentation covers aetiology of Parkinson’s disease.

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Neurobiology

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The motor cortex

Motor activity is controlled by projections that range from the primary motor cortex and the premotor cortical areas of the frontal lobe through to the brainstem and spinal cord.^{[Patestas & Gartner, 2016]} The primary motor cortex has an important function…

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Parkinsons Disease – Neurobiology and Aetiology – slide 4

The basal ganglia

Normal motor function is the result of complex and intricate interactions between the basal ganglia, the cerebellum, and the cerebral cortex.^{[Patestas & Gartner, 2016]} The main function of the basal ganglia is to initiate motor activity and to control cortical…

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Parkinsons Disease – Neurobiology and Aetiology – slide 5

The direct and indirect motor pathways

Direct motor pathway mechanism (facilitates movement) The direct motor pathway goes from the striatum to the globus pallidus interna (GPi) via fibres that inhibit GPi activity.^{[DeLong, 2000]} When this occurs, the GPi no longer inhibits the thalamus, which is now…

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Parkinsons Disease – Neurobiology and Aetiology – slide 6

Neurotransmitters and the presynaptic and postsynaptic neurons

Cells of the nervous system communicate with each other at synapses, either via electrical signals or by the release of messenger molecules called neurotransmitters.^{[Patestas & Gartner, 2016]} Examples of neurotransmitters include: acetylcholine, adrenaline, dopamine, serotonin, glutamate, and histamine.^{[Patestas & Gartner,…}

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The role of dopamine in the brain

Dopamine is an excitatory neurotransmitter present in the neurons of several regions of the central nervous system.^{[Patestas & Gartner, 2016]} The major dopamine-containing area is the corpus striatum, which plays a central role in the coordination of body movements.^{[Patestas &…}

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The pathogenesis of Parkinson’s disease

Parkinsons Disease – Neurobiology and Aetiology – slide 8

The pathogenesis of Parkinson’s disease

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Parkinsons Disease – Neurobiology and Aetiology – slide 9

Lewy bodies

A Lewy body is largely composed of misfolded, insoluble α‑synuclein.^{[Halliday et al., 2014]} There are, however, many other components of Lewy bodies, including structural fibril proteins, α‑synuclein-binding proteins, and cellular components normally involved in the degradation and recycling of proteins…

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Parkinsons Disease – Neurobiology and Aetiology – slide 10

α-synuclein

The protein α-synuclein was first isolated from human brain tissue during the early 1990s.^{[Burré, 2015]} Its role in PD only became apparent in 1997, when a mutation in the α-synuclein gene was discovered in groups affected by a rare, autosomal-dominant…

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Parkinsons Disease – Neurobiology and Aetiology – slide 11

Dopaminergic cell loss in Parkinson’s disease

The overall level of atrophy of brain tissue does not seem to differ between patients with PD and age-matched controls.^{[Halliday et al., 2014]} However, by the time a patient with PD develops motor symptoms, they will have suffered a moderate-to-severe…

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Parkinsons Disease – Neurobiology and Aetiology – slide 12

Braak staging of Parkinson’s disease

At a physiological level, PD is characterised by the loss of neurons in specific regions of the brain and a spreading of Lewy pathology.^{[Halliday et al., 2014]} However, these do not necessarily always go together; many regions with a concentration…

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Parkinsons Disease – Neurobiology and Aetiology – slide 13

Distribution of α-synuclein pathology in Parkinson’s disease

The Lewy pathology and aggregated α-synuclein proteins associated with PD are not confined to the central nervous system (CNS); they can also be found in the peripheral nervous system at various sites around the body, such as the skin, gastrointestinal…

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Parkinsons Disease – Neurobiology and Aetiology – slide 14

The gastrointestinal system and Parkinson’s disease

Neurons found in the enteric (gut) nervous system (ENS) require dopamine.^{[Rao & Gershon, 2016]} Without dopamine, these neurons cannot properly control gastrointestinal motility.^{[Rao & Gershon, 2016]}Animal studies have suggested that the ENS may be vulnerable to degeneration during PD,…

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