Altered dopamine homeostasis is an accepted mechanism in the pathogene-sis of Parkinson’s disease. a-Synuclein overexpression and impaired dis-posal contribute to this mechanism. However, biochemical alterations
associated with the interplay of cytosolic dopamine and increaseda-synuc-lein are still unclear.
Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition
Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài:
Nanomechanical properties of a-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM
Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Correction: Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition
Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated α-synuclein
Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: The acute inflammatory response to intranigral a-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation
The neurotransmitter dopamine has been shown to inhibit fibrillation of
a-synuclein by promoting the formation of nonamyloidogenic oligomers.
Fibrillation ofa-synuclein is accelerated in the presence of pesticides and
the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Accumulation ofa-synuclein resulting in the formation of oligomers and
protofibrils has been linked to Parkinson’s disease and Lewy body demen-tia. In contrast, b-synuclein (b-syn), a close homologue, does not aggregate
and reducesa-synuclein (a-syn)-related pathology.
a-synuclein is one of a family of proteins whose function remains
unknown. This protein has become linked to a number of neurodegenera-tive disease although its potential causative role in these diseases remains
mysterious. In diseases such as Parkinson’s disease and Lewy body demen-tias, a-synuclein becomes deposited in aggregates termed Lewy bodies.
a-Synuclein exists in two different compartments in vivo –
correspondingly existing as two different forms: a mem-brane-bound form that is predominantlya-helical and a
cytosolic form that is randomly structured. It has been sug-gested that these environmental and structural differences
may play a role in aggregation propensity and development
of pathological lesions observed inParkinson’s disease (PD).
Such effects may be accentuated by mutations observed in
familial PD kindreds.
The casein milk proteins and the brain proteinsa-synuclein
and tau have been described as natively unfolded with ran-domcoil structures,which, inthecaseofa-synucleinandtau,
have a propensity to form the ®brils found in a number of
neurodegenerative diseases. New insight into the structures
of these proteins has been provided by a Raman optical
activity study, supplemented with dierential scanning cal-orimetry, of bovineb-andj-casein, recombinant humana-,
Hyperphosphorylation of tau protein (tau) causes neurodegenerative dis-eases such as Alzheimer’s disease (AD). Recent studies of the physiological
correlation between tau and a-synuclein (a-SN) have demonstrated that:
(a) phosphorylated tau is also present in Lewy bodies, which are cyto-plasmic inclusions formed by abnormal aggregation ofa-SN
A yeast model was generated to study the mechanisms and phenotypical
repercussions of expression of a-synuclein as well as the coexpression of
protein tau. The data show that aggregation ofa-synuclein is a nucleation–
elongation process initiated at the plasma membrane. Aggregation is con-sistently enhanced by dimethyl sulfoxide, which is known to increase the
level of phospholipids and membranes in yeast cells.
Parkinson’s disease is characterized by the loss of dopaminergic neurons
in the nigrostriatal pathway accompanied by the presence of intracellular
cytoplasmic inclusions, termed Lewy bodies. Fibrillized a-synuclein forms
the major component of Lewy bodies. We reported a specific interaction
between rata-synuclein and tat binding protein 1, a subunit of PA700, the
regulatory complex of the 26S proteasome.
Fibrillization ofa-synuclein (a-Syn) is closely associated with the formation
of Lewy bodies in neurons and dopamine (DA) is a potent inhibitor for
the process, which is implicated in the causative pathogenesis of Parkin-son’s disease (PD). To elucidate any molecular mechanism that may have
biological relevance, we tested the inhibitory abilities of DA and several
analogs including chemically synthetic and natural polyphenols in vitro.
The last decade has seen clear links emerge between the genetic determi-nants and neuropathological hallmarks of parkinsonism and dementia,
notably with the discovery of mutations ina-synuclein and tau. Following
the description of mutations in LRRK2 linked to Parkinson’s disease, char-acterized by variable pathology including eithera-synuclein or tau deposi-tion, it has been suggested that LRRK2 functions as an upstream regulator
of Parkinson’s disease pathogenesis.
The molecular chaperone,a-crystallin, has the ability to prevent the fibril-lar aggregation of proteins implicated in human diseases, for example,
amyloidbpeptide anda-synuclein. In this study, we examine, in detail,
two aspects of a-crystallin’s fibril-suppressing ability: (a) its temperature
dependence, and (b) the nature of the aggregating species with which it