Emerging and potential therapies for Alzheimer's disease. 2008

Heledd H Griffiths, and Isobel J Morten, and Nigel M Hooper
University of Leeds, Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Leeds Institute of Genetics, Health and Therapeutics, Leeds LS2 9JT, UK.

BACKGROUND The amyloid beta (Abeta) peptide is critical to the development of Alzheimer's disease (AD), the major neurodegenerative disease of the elderly for which there is currently no cure. OBJECTIVE To review the literature on emerging treatments and potential therapeutic strategies for AD. METHODS Available published literature and information from pharmaceutical companies was utilised. CONCLUSIONS Several of the current treatments to combat AD are aimed at inhibiting the production, blocking the oligomerisation/aggregation or enhancing the degradation of Abeta. In our opinion, albeit based on limited available data, a future potential therapeutic strategy is to mimic the mechanism by which the normal cellular form of the prion protein inhibits the beta-secretase beta-site amyloid precursor protein cleaving enzyme-1 (BACE1), and hence the production of Abeta.

UI MeSH Term Description Entries
D011328 Prions Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL. Mink Encephalopathy Virus,Prion,Encephalopathy Virus, Mink
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016282 Aspartic Acid Endopeptidases A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity. Aspartic Endopeptidases,Aspartyl Endopeptidases,Acid Endopeptidases, Aspartic,Endopeptidases, Aspartic Acid,Endopeptidases, Aspartyl
D016564 Amyloid beta-Protein Precursor A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES. Amyloid A4 Protein Precursor,Amyloid Protein Precursor,beta-Amyloid Protein Precursor,Amyloid beta Precursor Protein,Protease Nexin 2,Protease Nexin II,Amyloid beta Protein Precursor,Nexin 2, Protease,Nexin II, Protease,beta Amyloid Protein Precursor,beta-Protein Precursor, Amyloid
D053829 Amyloid Precursor Protein Secretases Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave. APP Secretase,Amyloid Precursor Protein Secretase,Secretase,Secretases,alpha-Secretase,beta-Secretase,gamma-Secretase,Secretase, APP,alpha Secretase,beta Secretase,gamma Secretase

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