Parkinson’s Disease: Disorder of Shaking Palsy

Parkinson’s disease is a progressively deteriorating disorder which affects the CNS; especially substantia nigra compacta located in both basal ganglia and brainstem. Substantia nigra compacta is consist with dopaminergic neurons. These DA neurons create dopamine; the main neurochemical originate in our body. DA signaling, chemical transmitter plays key role on both motivation and reward system; activated by ventral tegmental area (VTA), Balance and motor movement; activate basal ganglia (BG), red nucleus, reticular formation, substantia nigra (SNc), and cerebellum which are part of extrapyramidal system. In this paper, we are going to see how extrapyramidal system for movement get disrupted continuously due to lack of dopamine in brain; leading to the ailment named Parkinson’s.

Every known conditions of Parkinson’s disease probably emerge from a intricate interaction of territorial influence and genomic makeup. These conditions are classified as sudden and occur in populace with no apparent history of the disorder in their family. The causes of the sporadic cases remain unclear as they still under speculation. Around 15% of populace with Parkinson’s have family history of this disorder which make this disease succeed. Similar cases of Parkinson’s disease can be caused by changes in the LRRK2, PARK7, PINK1, PRKN, or SNCA gene trigger PD in togetherness with other factors; such as differences in food consumption and environment.

Parkinson’s disease is succeeded in an autosomal recessive pattern. This type of inheritance means that two copies of the gene in each cell are altered. Almost always, parents of an individual with an autosomal recessive Parkinson’s disease each carry one copy of the altered gene but do not show any indications of the disorder. Mutations occurs when transcription in cells goes wrong leading to malformed proteins. Transcription is a process which segment of the gene expression where our Deoxyribonucleic Acid (DNA) segment transcribed or copied into messenger Ribonucleic Acid (mRNA); and the mRNA which created from this procedure play a key role on protein synthesis. It is a tedious but yet so complex process which happens in every living cells. Through enhancing and regulating meticulously create mature mRNA that can work as coding for amino acid; just like building a house.

Parkinson’s is the second well-known nervous disorder in human; characterized by aggregation of the protein, α-synuclein .This protein play key role in kinase domain; and can be malfunctioned due to alteration during RNA transcription occurring within SNCA gene. As a result, α-synuclein proteins become clusters known as Lewy bodies; and can render it to be non-functional. These malformed protein clusters can be presented in varied brain region and can cause other nervous disorder, Accumulation of Lewy bodies in neural cell in dopaminergic SNc lead to more profound non motor symptom; preceding the motor symptom in PD victims. Using gene remedy on early stage might prevent the Parkinson’s as there is no known cure for it yet. The most important pathological feature caused by α-synuclein aggregation is the disruption of calcium (Ca2+) homeostasis.

Calcium is an essential ion required for adaptive nature of the cell as they involve in many of the cellular function such as neural network, second messenger and vesicular docking. The intracellular level of calcium ion concentration lower in in comparison to extracellular area. This concentration variation give rise to the driving force to neural signaling which lead to quick adaptation. L-type of calcium channels are high voltage gated channel (Cav1 family) which involve in burst firing and rhythmic pace making.

As of today, research shows that Dopamine neuron in striatum require pace making signaling to maintain the DA level. Unlikely to Cav1 .2, Cav1,3 type of channels that are involved in peacemaking in above process have wider opening range causing it to not able to completely close itself. Because of that, more calcium influx happen internally. Because of the sudden increase in Calcium influx, the intracellular calcium concentration increase abnormally in which cells become less capable of bring forth homeostasis within itself and more Cav1.3 channel get expressed through striatum DA neurons causing more calcium influx. This constant exposure leads to apoptosis; or cell death of the DA producing neuronal cells.

Currently, patients have no known remedy, but the therapeutics like precursor L-dopa, dopamine agonist, MAOI inhibitors, and anticholinergic are being used to alleviate the manifestation. Familiar symptom of Parkinson’s disease is shake (tremble) of a limb. Other characteristic traits of Parkinson’s disease are inflexible of the limbs and torso, “bradykinesia “or an “akinesia”, and impaired postural stability. These prodromes become noticeable slowly over time. Sporadic condition of ailment make it harder to age restrict; but most people recognized are over the age of 50 when detected or when the trait manifest(late onset). Also there are patients with early onset (before age of 50) and even juvenile onset (before age of 20) which rise to the question on how well we know our genome. As I previously stated, this disorder affected by the dopamine level as they triggered by extinction of DA neuronal cells in substantia nigra compacta; which in turn affect several regions in one’s brain. Due to the crucial of DA level in neural connection as whole, PD not only affect motion, emotion, and cognition. Parkinson’s Disease is estimated to be affecting more than one million Americans; and approximately sixty thousand people get identified with Parkinson’s disease; annually in America.

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