Amyloid P Component Promotes Aggregation of Alzheimer′s β-Amyloid Peptide

Hamazaki, Hideaki

doi:10.1006/bbrc.1995.1819

Cited by 51 publications

(36 citation statements)

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“…6, 1997 of amyboid P component on A/I amyloid fibril formation. One study suggested that P component was a potent promoter of A/I fibril formation (Hamazaki, 1995), whereas another study suggested that it was an inhibitor of A/I fibri! formation .…”

Section: Discussionmentioning

confidence: 99%

Perlecan Binds to the β‐Amyloid Proteins (Aβ) of Alzheimer's Disease, Accelerates Aβ Fibril Formation, and Maintains Aβ Fibril Stability

Castillo

Ngo

Cummings

et al. 1997

Journal of Neurochemistry

247

177

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Section: Discussionmentioning

confidence: 99%

Perlecan Binds to the β‐Amyloid Proteins (Aβ) of Alzheimer's Disease, Accelerates Aβ Fibril Formation, and Maintains Aβ Fibril Stability

Castillo

Ngo

Cummings

et al. 1997

Journal of Neurochemistry

247

177

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“…At these low levels, clusterin was found incorporated into insoluble A and SH3 fibrils. 28 Similarly, at low SAP:A ratios, SAP promoted the formation of Aβ aggregates; 99 at SAP:A of 1:1000, short fibrillar-like structures lacking typical amyloid features were formed which often contained associated SAP molecules. 95 In addition,  2 M has been shown to stabilize a conformation of the prion protein resistant to proteinase K (PrPRes) that is thought to initiate aggregation and is associated with prion disease pathology.…”

Section: Effects Of Ecs On Amyloid Formation In Vitromentioning

confidence: 99%

Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity

2008

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The in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors may be critical parts of a quality control system to protect the body against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. Keywords: Extracellular chaperones, receptor-mediated endocytosis, amyloid, protein quality control, aggregate toxicity, fibril formation word statement (for Contents list) plus graphic (note -colour version of below graphic provided separately)Newly identified abundant extracellular chaperones (ECs) may protect the body against dangerously hydrophobic proteins/peptides. This review proposes that ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. SUMMARYThe in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors may be critical parts of a quality control system to protect the body against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

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“…At these low levels, clusterin was found incorporated into insoluble Aβ and SH3 fibrils . Similarly, at low SAP:Aβ ratios, SAP promoted the formation of Aβ aggregates (Hamazaki 1995); at SAP:Aβ of 1:1000, short fibrillar-like structures lacking typical amyloid features were formed which often contained associated SAP molecules (Janciauskiene et al, 1995). In addition, α 2 M has been shown to stabilize a conformation of the prion protein resistant to proteinase K (PrPRes) that is thought to initiate aggregation and is associated with prion disease pathology (Adler and Kryukov 2007).…”

Section: Effects Of Ecs On Amyloid Formation In Vitromentioning

confidence: 99%

“…One poorly understood pathway relates to the observation that under some conditions ECs can actually promote the formation of amyloid fibrils; clusterin, α2M and SAP have been shown to promote fibril formation in vitro (Hamazaki 1995;Adler and Kryukov 2007;Yerbury et al, 2007) (see section 4.1). In addition, in a transgenic mouse model expressing APP (PDAPP mice), a comparison of clusterin -/-and clusterin +/+ mice showed no difference in the amount of Aβ deposited in the brain, however the amount of thioflavin S positive material was larger in clusterin +/+ mice (DeMattos et al, 2002).…”

Section: When Quality Control Is Compromised?mentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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The pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacerabate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ABSTRACTThe pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

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Amyloid P Component Promotes Aggregation of Alzheimer′s β-Amyloid Peptide

Cited by 51 publications

References 0 publications

Perlecan Binds to the β‐Amyloid Proteins (Aβ) of Alzheimer's Disease, Accelerates Aβ Fibril Formation, and Maintains Aβ Fibril Stability

Perlecan Binds to the β‐Amyloid Proteins (Aβ) of Alzheimer's Disease, Accelerates Aβ Fibril Formation, and Maintains Aβ Fibril Stability

Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity

Extracellular Chaperones and Amyloids

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