Cited by 223Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

Interaction between Aβ Peptide and α Synuclein: Molecular Mechanisms in Overlapping Pathology of Alzheimer’s and Parkinson’s in Dementia with Lewy Body Disease

Mandal, Pravat K., Pettegrew, Jay W., Masliah, Eliezer, Hamilton, Ronald L., Mandal, Ratna·2006·Neurochemical Research

Abstract

Amyloidogenic proteins (Abeta peptide) in Alzheimer's disease (AD) and alpha-synuclein (alpha-Syn) in Parkinson's disease (PD) are typically soluble monomeric precursors, which undergo remarkable conformational changes and culminate in the form of aggregates in diseased condition. Overlap of clinical and neuropathological features of both AD and PD are observed in dementia with Lewy body (DLB) disease, the second most common form of dementia after AD. The identification of a 35-amino acid fragment of alpha-Syn in the amyloid plaques in DLB brain have raised the possibility that Abeta and alpha-Syn interact with each other. In this report, the molecular interaction of alpha-Syn with Abeta40 and/or Abeta42 are investigated using multidimensional NMR spectroscopy. NMR data in the membrane mimic environment indicate specific sites of interaction between membrane-bound alpha-Syn with Abeta peptide and vice versa. These Abeta-alpha-Syn interactions are demonstrated by reduced amide peak intensity or change in chemical shift of amide proton of the interacting proteins. Based on NMR results, the plausible molecular mechanism of overlapping pathocascade of AD and PD in DLB due to interactions between alpha-Syn and Abeta is described. To the best of our knowledge, it is the first report using multidimensional NMR spectroscopy that elucidates molecular interactions between Abeta and alpha-Syn which may lead to onset of DLB.

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Crossref · 10.1007/s11064-006-9140-9

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  • Evidence suggests that Aβ can directly affect α-synuclein toxicity, and tau protein and α-synuclein can directly interact promoting their co-assembly.

    “Evidence suggests that Aβ can directly affect α-synuclein toxicity, and it is also known that tau protein and α-synuclein can directly interact promoting their co-assembly [124–126].”

    From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [124]

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Authors
Mandal, P. K., Pettegrew, J. W., Masliah, E., Hamilton, R. L., & Mandal, R.
Affiliations
  • University of Pittsburgh Medical Center (US)
  • University of California San Diego (US)
  • University of Pittsburgh (US)
Corresponding author
Mandal, Pravat K.
Venue
Neurochemical Research
Published
2006-09
Volume
31
Issue
9
Pages
1153-1162
ISSN
  • 0364-3190 (ISSN-L)
  • 1573-6903
OpenAlex
W1965229261
Cited by
219
References
48
Citations by year
2026: 4 · 2025: 10 · 2024: 8 · 2023: 12 · 2022: 12 · 2021: 17 · 2020: 20 · 2019: 17 · 2018: 7 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 9 · 2013: 11 · 2012: 9
FWCI
6.34
Type
journal article
Language
en
Open access
closed
Locations
  • Neurochemical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, alpha-synuclein, dementia with Lewy bodies, Alzheimer's disease, Parkinson's disease, protein-protein interaction, Aβ40, amyloid-beta 42, amyloid plaques, protein aggregation, molecular pathogenesis
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Brain, Humans, Molecular Sequence Data, Parkinson Disease, Peptide Fragments, Amyloid beta-Peptides, Nuclear Magnetic Resonance, Biomolecular, Lewy Body Disease, alpha-Synuclein

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