Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration

Nathaniel G N Milton

doi:10.1007/0-387-23226-5_20

Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration

Nathaniel G N Milton

Research output: Contribution to journal › Review article › peer-review

22 Citations (Scopus)

Abstract

Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Abeta phosphorylation by the CDK-1 inhibitor olomoucine prevented Abeta toxicity, suggesting that the phosphorylated Abeta peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Abeta toxicity.

The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target.

Original language	English
Pages (from-to)	381-402
Number of pages	22
Journal	Subcellular Biochemistry
Volume	38
DOIs	https://doi.org/10.1007/0-387-23226-5_20
Publication status	Published - 2005
Externally published	Yes

Keywords

Alzheimer Disease/pathology
Amyloid beta-Peptides/metabolism
Animals
Cyclin-Dependent Kinases/antagonists & inhibitors
Enzyme Inhibitors/therapeutic use
Humans
Kinetin
Nerve Degeneration/pathology
Phosphoproteins/antagonists & inhibitors
Phosphorylation
Purines/therapeutic use

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10.1007/0-387-23226-5_20

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title = "Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration",

abstract = "Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Abeta phosphorylation by the CDK-1 inhibitor olomoucine prevented Abeta toxicity, suggesting that the phosphorylated Abeta peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Abeta toxicity. The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target.",

keywords = "Alzheimer Disease/pathology, Amyloid beta-Peptides/metabolism, Animals, Cyclin-Dependent Kinases/antagonists & inhibitors, Enzyme Inhibitors/therapeutic use, Humans, Kinetin, Nerve Degeneration/pathology, Phosphoproteins/antagonists & inhibitors, Phosphorylation, Purines/therapeutic use",

author = "Milton, {Nathaniel G N}",

note = "Volume 38 is called Alzheimer's Disease",

year = "2005",

doi = "10.1007/0-387-23226-5_20",

language = "English",

volume = "38",

pages = "381--402",

journal = "Subcellular Biochemistry",

issn = "0306-0225",

publisher = "Springer Nature",

}

TY - JOUR

T1 - Phosphorylated amyloid-beta

T2 - the toxic intermediate in alzheimer's disease neurodegeneration

AU - Milton, Nathaniel G N

N1 - Volume 38 is called Alzheimer's Disease

PY - 2005

Y1 - 2005

N2 - Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Abeta phosphorylation by the CDK-1 inhibitor olomoucine prevented Abeta toxicity, suggesting that the phosphorylated Abeta peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Abeta toxicity. The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target.

AB - Phosphorylated Amyloid-beta (Abeta) was identified in Alzheimer's disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Abeta phosphorylation. The phosphorylated Abeta peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Abeta phosphorylation by the CDK-1 inhibitor olomoucine prevented Abeta toxicity, suggesting that the phosphorylated Abeta peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Abeta toxicity. The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target.

KW - Alzheimer Disease/pathology

KW - Amyloid beta-Peptides/metabolism

KW - Animals

KW - Cyclin-Dependent Kinases/antagonists & inhibitors

KW - Enzyme Inhibitors/therapeutic use

KW - Humans

KW - Kinetin

KW - Nerve Degeneration/pathology

KW - Phosphoproteins/antagonists & inhibitors

KW - Phosphorylation

KW - Purines/therapeutic use

U2 - 10.1007/0-387-23226-5_20

DO - 10.1007/0-387-23226-5_20

M3 - Review article

C2 - 15709490

SN - 0306-0225

VL - 38

SP - 381

EP - 402

JO - Subcellular Biochemistry

JF - Subcellular Biochemistry

ER -

Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration

Abstract

Keywords

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