Examining the Toxicity of α-Synuclein in Neurodegenerative Disorders

Abstract

α-synuclein is considered the main pathological protein in a variety of neurodegenerative disorders, such as Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. As of now, numerous studies have been aimed at examining the post-translational modifications of α-synuclein to determine their effects on α-synuclein aggregation, propagation, and oligomerization, as well as the potential cellular pathway dysfunctions caused by α-synuclein, to determine the role of the protein in disease progression. Furthermore, α-synuclein also appears to contribute to the fibrilization of tau and amyloid beta, which are crucial proteins in Alzheimer’s disease, advocating for α-synuclein’s preeminent role in neurodegeneration. Due to this, investigating the mechanisms of toxicity of α-synuclein in neurodegeneration may lead to a more proficient understanding of the timeline progression in neurodegenerative synucleinopathies and could thereby lead to the development of potent targeted therapies.

In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration

“…Although various cell functions of α-syn remain to be established, the protein is known to be involved in some neurodegenerative disorders [ 7 ]. In fact, α-syn is a major component of Lewy bodies [ 8 , 9 , 10 , 11 ] in Parkinson’s disease (PD), and it is often detected in Alzheimer’s disease [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Data about the occurrence of the syns family in tumors mostly investigated γ-syn, which may be aberrantly expressed [ 19 ].…”

Distinguishing features of depression in dementia from primary psychiatric disease

“…It is well accepted that protein aggregations define most dementias neuropathologically, and accumulating evidence suggests a causal role for these proteinopathies in dementia progression [86]. Specifically, amyloid-beta (Aβ) is associated with AD [87]; hyperphosphorylated tau (p-tau) with AD and frontotemporal dementia [88]; alpha-synuclein with Dementia with Lewy Bodies and Parkinson's Disease Dementia [89]; and TAR DNA-binding protein 43 (TDP-43) with Frontotemporal Dementia and Limbic predominant Age-related TDP-43 Encephalopathy (LATE) [90]. In addition, positron emission tomography (PET) tracers that bind to these pathological aggregates are gaining traction in clinical practice after being employed in research for many years [91][92][93][94].…”