Keywords

Parkinsons, Drosophilia, Neurodegenerative Disease

Disciplines

Medical Neurobiology | Neurology

Mentor

Dr. Sok Kean Khoo

Abstract

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases. It is characterized by its main symptom of a tremor that usually starts in one limb. The four cardinal symptoms of PD are tremor, rigidity, bradykinesia, and postural instability. While the four cardinal symptoms are all motor symptoms there are non-motor symptoms for PD which include cognitive changes, sleeping disorders, lightheadedness, early satiety, and mood disorders. PD is characterized by dopaminergic (DA) neuron loss and the accumulation of Lewy bodies (LB) which are predominantly composed of α-synuclein (α-Syn) protein.

α-Syn is a protein found abundantly in the brain. It is characterized by an amphipathic lysine-rich amino terminus which plays a role in modulating its interactions with membranes. This protein is also characterized by its acidic carboxy-terminal tail, which plays a role in regulating its nuclear localization and interactions with metals, small molecules and proteins (Lashuel et al.). The misfolding of α-Syn can cause aggregates allowing damage to the cells that it is found in, which has been shown to be a cause of PD. Mutation in α-Syn was first noted in 1997, where an amino acid substitution change was noted producing an autosomal-dominant pattern of inheritance for PD (Stefanis). There are two types of PD, familial PD where a mutation can be passed on through generations. Sporadic PD, the second type of PD, is when the mutations occur in patients without the familial connection to PD. Mutations in the leucine-rich repeat kinase 2 (LRRK2) have also been linked to the cause of autosomal dominant PD. Additionally, LRRK2 has been linked to tau and α-Syn pathologies, suggesting that possibly LRRK2 mutations are players in cell degeneration or cell death. Mitochondrial dysfunction can also lead to PD, therefore the pathway that leads to this dysfunction needs to be explored more.

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