Synucleinopathy

Introduction[edit|edit source]

Synucleinopathies are a subgroup ofneurodegenerative diseases, characterised by impairment of alpha-synuclein (αSyn) metabolism, producing abnormal intracellular deposits (namely progressive aggregation of insoluble fibrillary αSyn inneuronsandglia). All of them arechronic, progressive disorders that lack a causal therapy.^[1][2]

Although the exact mechanism of initiation of aggregation and misfolding pathway of a-Syn is yet to be discovered; it’s mechanism of spreading through interconnected neuronal networks is a proposed theory. This theory suggests that a-Syn is released from the diseased cell and is then uptaken by normal adjacent cells.^[3][4]

Divisions Of Synucleinopathies[edit|edit source]

The synucleinopathies can be divided into those with and those without the formation of Lewy bodies (however some overlap does exist) and include:

1. Synucleinopathies路易小体:Parkinson disease(PD);Lewy body disease(LBD);
2. Synucleinopathies without Lewy bodies:Multiple systemic atrophy(MSA); pure autonomic failure; rapid eye movement (REM)sleepbehaviour disorder.^[1]

This 4 minute video gives a introduction to the synucleinopathies

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Human Alpha-Synuclein (α-syn)[edit|edit source]

Human alpha-synuclein (α-syn) is predominantly expressed in thebrain, accounting for approximately 1% of brain weight. It is found chiefly in the neocortex,hippocampus,substantia nigra,thalamus,cerebellum,is found in Lewy bodies (LBs). As well as accumulating in the brain, α-synuclein also accumulates in the gastrointestinal tract resulting in symptoms.^[6][1][3]

Main Symptoms[edit|edit source]

Synucleinopathies are chronic disorders that develop gradually. Symptoms include:

1. A decline in motor andcognitive功能
2. Behavioral changes.

Symptoms of these diseases significantly overlap with one another, hindering diagnosis. for exampleparkinsonismis the predominant symptom of PD. Still, it can be indistinguishable from the parkinsonism of LBD and MSA.^[7][2]

Diagnosis[edit|edit source]

A new tool developed to reveal abnormal alpha -synuclein in brain and body cells has shown high potential to differentiate people with Parkinson's disease from healthy controls..^[8]In a cross-sectional analysis of 1123 participants, sensitivity for Parkinson's disease was 87·7% (95% CI 84·9–90·5), and specificity for healthy controls was 96·3% (93·4–99·2). The sensitivity of the α-synuclein SAA in sporadic Parkinson's disease with the typical olfactory deficit was 98·6% (96·4–99·4).^[8]

Future Management[edit|edit source]

In healthy brain cells, correctly constructed alpha synuclein is typically found just inside the surface of the membrane surrounding the cell body and in the presynaptic terminals (critical to passing messages between neurons).^[9]

The abnormal aggregation of α-synuclein has proved to be the “rosetta stone” of PD, DLB, and MSA. There is increasing evidence demonstrating the propagation of pathological α-Syn to be central to the pathogenesis of synucleinopathies, for example in PD and MAS.^[2][6]

Comprehending disease aetiology and pathogenesis is a start, but developing safe and effective mechanism-based treatments is the goal. For example, some pharmaceutical companies are focusing on compounds that prevent α-syn from aggregation. When mechanism-based therapies for PD, LBD, and MSA will become available, they will probably interfere with the neurodegeneration caused by the aggregation of α-synuclein.^[10]

References[edit|edit source]