Lewy bodies are spherical, intracytoplasmic, eosinophilic, neuronal inclusions comprising abnormally truncated and phosphorylated intermediate neurofilament proteins, alpha-synuclein, ubiquitin, and associated enzymes. The clinical presentation of LB disease varies according to the site of LB formation and associated neuronal loss. Three main clinicopathological syndromes have been described--movement disorder, autonomic failure, and dementia. Parkinsonism is the most common presentation of LB disease developing in middle life. In older patients, a mixture of cognitive, autonomic, and motor dysfunction is more common. Dementia with LB (DLB) is a relatively recently described clinicopathological syndrome that accounts for up to 20% of all cases of dementia in old age. Patients, typically in their seventh and eighth decades, have LB pathology in cortical neurons as well as in the brain stem. LB disease should be considered in the differential diagnosis of a wide range of clinical presentations including episodic disturbances of consciousness, syncope, sleep disorders, and unexplained delirium.
"Autonomic dysfunction is common clinical symptoms in neurodegenerative disorders including Lewy body disease and taupathy.1,11 Especially, in the disorders involving dysregulation of alpha-synuclein, symptoms result from degeneration in autonomic regulatory regions of the brain or peripheral autonomic ganglia.12 "
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose:
Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ).
Total 259 patients, including 192 patients with [idiopathic Parkinson’s disease (IPD, age 64.6 ± 9.6 years)], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3)], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6)]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension.
Although dementia with Lewy body (DLB) patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8) were significantly increased than that of IPD (15.1 ± 10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP.
Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD.
"These include dementia with LB, the second major cause of dementia after AD  , the Lewy body variant of Alzheimer's disease   , multiple system atrophy , and neurodegeneration with brain iron accumulation type 1 . Human -synuclein is a 140 amino acid protein of unknown function that is abundantly expressed in the brain, where it is concentrated in presynaptic nerve terminals  . "
[Show abstract][Hide abstract] ABSTRACT: The protein alpha-synuclein plays an important role in many neurodegenerative disorders, referred to as alpha-synucleinopathies, that include, among others, Parkinson's and Alzheimer's diseases. The central region of the wild type protein, known as the non-Abeta component of amyloid plaques (NAC, amino acids 61-95), seems to be responsible for its aggregation process. To structurally characterize this fragment by nuclear magnetic resonance, we produced it by DNA recombinant technology. This technique, unlike chemical synthesis, allows the production of labeled samples (13C, 15N) required for NMR studies. Because the NAC region is very sparingly soluble in aqueous buffer, we cloned a slightly larger portion of alpha-synuclein, alphasyn57-102, with the presence of several charged residues in both extremities of the NAC region. The conformational preferences of purified alphasyn57-102, in solution and bound to SDS micelles, was studied. Our results indicate that the protein is largely unfolded in solution but exhibits a helical conformation in the lipid-associated state. The methodology that we have used in this work for the cloning, expression, and purification of alphasyn57-102 can be easily applied to most small proteins, thus representing a powerful tool for structural NMR analysis of labeled peptides.
Protein Expression and Purification 02/2005; 39(1):90-6. DOI:10.1016/j.pep.2004.09.018 · 1.70 Impact Factor
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