Lewy Bodies in the Amygdala

Popescu, Anca; Lippa, Carol F.; Lee, Virginia M.‐Y.; Trojanowski, John Q.

doi:10.1001/archneur.61.12.1915

Cited by 108 publications

(32 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, the present data suggest that parkin might be protective in certain conditions such as PSP and other tauopathies but lack any protective role in conditions such as FTD-P, where the P301L mutant seems to be a causal factor in the disease (Hutton et al 1998). Furthermore, a notable increase in total τ levels was observed in the presence of α-synuclein and β-amyloid, consistent with previous findings in both AD and PD (Popescu et al 2004;Lippa et al 2005). The increase in total τ levels was counteracted with parkin, consistent with cell viability data.…”

Section: Discussionsupporting

confidence: 91%

“…Parkin has been shown to decrease the intracellular levels of β-amyloid (Rosen et al 2006). Immunoreactivity to parkin and crosslinking between parkin, ubiquitin, α-synuclein, and τ as well as parkin, β-amyloid, and τ have been observed in the tauopathies and Lewy body diseases (Nemes et al 2004;Layfield et al 2003;Paviour et al 2004;Popescu et al 2004;Lippa et al 2005;Pletnikova et al 2005). Therefore, a possible parkin effect on amyloid levels may also be a contributing factor to parkin's ability to counteract the incitement of intracellular amyloids on GSK-3β activation and τ hyperphosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, τ and α-synuclein coaggregate in Lewy bodies (Ishizawa et al 2003;Yancopoulou et al 2005). Abnormal aggregates of α-synuclein, β-amyloid, and τ are found in neurodegenerative diseases with secondary Lewy bodies (Popescu et al 2004;Lippa et al 2005). Aβ deposition can also be associated with increased cortical α-synuclein regions in PD and Lewy bodies with dementia (Pletnikova et al 2005).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Parkin Attenuates Wild-Type τ Modification in the Presence of β-Amyloid and α-Synuclein

Moussa

2008

J Mol Neurosci

View full text Add to dashboard Cite

Changes in tau (tau) metabolism comprise important pathological landmarks in the tauopathies with parkinsonism as well as Parkinson's disease and Alzheimer's disease. Mutations in the parkin gene are associated with Parkinson's disease. Deposits of amyloid proteins, including Abeta and alpha-synuclein coexist in the brains of patients with dementia with Lewy bodies; however, it is not known how either of them interacts with tau to provoke neurofibrillary tangle formation across the tauopathies. Here, we show a role for parkin against tau pathology in the presence of intracellular Abeta or alpha-synuclein. Parkin attenuates four-repeat human tau, but not mutant P301L, hyperphosphorylation in the presence of intracellular Abeta(1-42), or alpha-synuclein and decreases GSK-3beta activity in amyloid-stressed M17 human neuroblastoma cells. These data suggest that parkin may counteract the alteration of tau metabolism in certain neurodegenerative diseases with tau cytopathy and parkinsonism.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Parkin Attenuates Wild-Type τ Modification in the Presence of β-Amyloid and α-Synuclein

Moussa

2008

J Mol Neurosci

View full text Add to dashboard Cite

show abstract

“…LB occur in a number of other neurological disorders, including LB dementia (LBD) (13,14); Alzheimer's disease (AD) (15), including cases of familial AD with mutations in the presenilin 1,2 and amyloid precursor protein genes (16); Down's syndrome (17); neurodegeneration with brain iron accumulation type 1 (also known as Hallervorden-Spatz disease) (18); progressive autonomic failure (19); rapid eye movement sleep disorder (20); Parkinsonism-dementia complex of Guam (21); Gaucher's disease (22); and Pick's disease (23).…”

mentioning

confidence: 99%

Lewy bodies

Shults

2006

Proc. Natl. Acad. Sci. U.S.A.

408

277

View full text Add to dashboard Cite

Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to ␣-synuclein (␣-SYN), which appears to be the major component of LB. The propensity for ␣-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of ␣-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of ␣-SYN could induce mitochondrial dysfunction and͞or release of proapoptotic molecules is proposed.

show abstract

“…Collectively, these disorders have been referred to as being synucleinopathies (4,5), with the vast majority of synucleinopathies being sporadic in nature. Familial forms of most synucleinopathies have also been documented, with strong experimental and genetic evidence indicating that many familial forms of synucleinopathy disorders are mediated by the presence of mutations in ␣-synuclein (6,7).…”

mentioning

confidence: 99%

α-Synuclein Alters Proteasome Function, Protein Synthesis, and Stationary Phase Viability

Chen

Thorpe

Keller

2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

␣-Synuclein appears to play a role in mediating neurotoxicity in a number of neurodegenerative disorders, collectively referred to as synucleinopathies. Most of these disorders are associated with aging and a probable impairment of the proteasome-proteolytic pathway, although the relationship between aging, proteasome inhibition, and ␣-synuclein toxicity has not been fully elucidated. Recent studies suggest that yeast may provide a useful system for studying the biology and toxicity of ␣-synuclein in mitotic cells, recapitulating many features observed in the various synucleinopathy disorders. Additional studies indicate that the stationary phase model of aging in yeast provides a useful system for understanding the biochemistry and regulation of aging in post-mitotic cells. In the present study we examined the effect of wild type and mutant ␣-synuclein (A30P) on multiple aspects of proteasome homeostasis, protein synthesis, as well as the ability of cells to survive stationary phase aging. These data demonstrate that ␣-synuclein alters proteasome composition, impairs proteasome-mediated protein degradation, impairs protein synthesis, and impairs the ability of cells to withstand stationary phase aging. Interestingly, ␣-synuclein had little effect on intracellular proteasome content or protein ubiquitination, and did not increase the vulnerability of cells to a variety of stressors. Together, these data suggest that yeast may be useful for understanding the ability of ␣-synuclein to impair proteasome-mediated protein degradation, as well as for understanding the basis for age-related ␣-synuclein cytotoxicity.

show abstract

Lewy Bodies in the Amygdala

Abstract: Abnormal alpha-synuclein aggregation in the amygdala is disease selective, but not restricted to disorders of alpha-synuclein and beta-amyloid. Our data are compatible with the notion that tau aggregates predispose neurons to develop secondary LBs.

Cited by 108 publications

References 26 publications

Parkin Attenuates Wild-Type τ Modification in the Presence of β-Amyloid and α-Synuclein

Parkin Attenuates Wild-Type τ Modification in the Presence of β-Amyloid and α-Synuclein

Lewy bodies

α-Synuclein Alters Proteasome Function, Protein Synthesis, and Stationary Phase Viability

Contact Info

Product

Resources

About