نتایج جستجو برای: synuclein
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alpha-synuclein gene mutations are major underlying genetic defects known in familial juvenile onset Parkinson's disease (PD), and alpha-synuclein is a major constituent of Lewy Bodies, the pathological hallmark of PD. The normal cellular function of alpha-synuclein has been elusive, and its exact etiological mechanism in causing dopaminergic neuronal death in PD is also not clearly understood....
α-Synuclein is a key molecule in understanding the pathogenesis of neurodegenerative α-synucleinopathies such as Parkinson's disease. Despite extensive research, however, its precise function remains unclear partly because of a difficulty in immunoblotting detection of endogenous α-synuclein. This difficulty has largely restricted the progress for α-synucleinopathy research. Here, we report tha...
Lewy bodies are made from insoluble, phosphorylated a-synuclein, but the earliest changes that precipitate such pathology still remain conjecture. In this study, we quantify and identify relationships between the levels of the main pathologic form of phosphorylated a-synuclein over the course of Parkinson’s disease in regions affected early through to end-stage disease. Brain tissue samples fro...
-Synuclein is a small cytosolic protein of presynaptic nerve terminals composed of seven 11-residue repeats and a hydrophilic tail. -Synuclein misfolding and dysfunction may contribute to the pathogenesis of Parkinson’s disease and neurodegenerative dementias, but its normal folding and function are unknown. In solution, -synuclein is natively unstructured but assumes an -helical conformation u...
Parkin Deficiency Delays Motor Decline and Disease Manifestation in a Mouse Model of Synucleinopathy
In synucleinopathies, including Parkinson's disease, partially ubiquitylated alpha-synuclein species phosphorylated on serine 129 (P(S129)-alpha-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against alpha-synuclein-mediated toxicity in various models.We analyzed the effects of Parkin deficiency in a mous...
Analyses using antibodies directed against α-synuclein play a key role in the understanding of the pathologies associated with neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). However, the generation of antibodies against immunogens with significant sequence similarity to host proteins such as α-synuclein is often h...
The aberrant aggregation of α-synuclein in the brain is a hallmark of Parkinson's disease (PD). In vivo soluble α-synuclein occurs as a monomer and several multimers, the latter of which may be important for the biological function of α-synuclein. Currently, there is a lack of reproducible methods to compare α-synuclein multimer abundance between complex biological samples. Here we developed a ...
Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parki...
Parkinson’s disease is a neurodegenerative disorder that is caused by the loss of dopaminergic neurons in the substantia nigra. Misfolding of αsynuclein is thought to cause this selective cell death. In our α-synuclein yeast overexpression model, we previously demonstrated that α synuclein, is non-toxic to yeast, runs 8-10 kDa higher on protein gels and aggregates minimally in vivo. Recently, a...
Parkinson adalah penyakit neurodegeneratif yang meningkat lebih cepat daripada gangguan neurologis lainnya. Saat ini pengobatan menggunakan dopamine agonist dan levodopa, namun memiliki efek samping seperti menurunkan nafsu makan tidak berfokus pada pencegahan kematian neuron. Salah satu protein berperan dalam patogenesis dari α-synuclein, di mana agregasi misfolding bersifat toksik neuron sehi...
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