Key Peptides and Proteins in Alzheimer's Disease

B. Penke, F. Bogár, Gábor Paragi, János Gera, L. Fülöp

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Alzheimer's Disease (AD) is a form of progressive dementia involving cognitive impairment, loss of learning and memory. Different proteins (such as amyloid precursor protein (APP), β- amyloid (Aβ) and tau protein) play a key role in the initiation and progression of AD. We review the role of the most important proteins and peptides in AD pathogenesis. The structure, biosynthesis and physiological role of APP are shortly summarized. The details of trafficking and processing of APP to Aβ, the cytosolic intracellular Aβ domain (AICD) and small soluble proteins are shown, together with other amyloid-forming proteins such as tau and α-synuclein (α-syn). Hypothetic physiological functions of Aβ are summarized. The mechanism of conformational change, the formation and the role of neurotoxic amyloid oligomeric (oAβ) are shown. The fibril formation process and the co-existence of different steric structures (U-shaped and S-shaped) of Aβ monomers in mature fibrils are demonstrated. We summarize the known pathogenic and non-pathogenic mutations and show the toxic interactions of Aβ species after binding to cellular receptors. Tau phosphorylation, fibrillation, the molecular structure of tau filaments and their toxic effect on microtubules are shown. Development of Aβ and tau imaging in AD brain and CSF as well as blood biomarkers is shortly summarized. The most probable pathomechanisms of AD including the toxic effects of oAβ and tau; the three (biochemical, cellular and clinical) phases of AD are shown. Finally, the last section summarizes the present state of Aβ- and tau-directed therapies and future directions of AD research and drug development.

Original languageEnglish
Pages (from-to)577-599
Number of pages23
JournalCurrent protein & peptide science
Volume20
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Alzheimer Disease
Peptides
Amyloid beta-Protein Precursor
Poisons
Proteins
Amyloid
Synucleins
Amyloidogenic Proteins
Serum Amyloid A Protein
tau Proteins
Phosphorylation
Biosynthesis
Memory Disorders
Biomarkers
Molecular Structure
Microtubules
Molecular structure
Dementia
Brain
Blood

Keywords

  • AD drugs
  • AD-pathomechanisms
  • Alzheimer's disease
  • amyloid aggregation
  • ApoE
  • APP
  • Tau
  • β-amyloid.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Key Peptides and Proteins in Alzheimer's Disease. / Penke, B.; Bogár, F.; Paragi, Gábor; Gera, János; Fülöp, L.

In: Current protein & peptide science, Vol. 20, No. 6, 01.01.2019, p. 577-599.

Research output: Contribution to journalArticle

Penke, B. ; Bogár, F. ; Paragi, Gábor ; Gera, János ; Fülöp, L. / Key Peptides and Proteins in Alzheimer's Disease. In: Current protein & peptide science. 2019 ; Vol. 20, No. 6. pp. 577-599.
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