Analysis of Amyloid Precursor Protein Function in Drosophila Melanogaster

Overview

Journal Exp Brain Res

Specialty Neurology

Date 2011 Sep 14

PMID 21912928

Citations 19

Authors

Burkhard Poeck

Roland Strauss

Doris Kretzschmar

Affiliations

Soon will be listed here.

Abstract

Amyloid precursor proteins (APPs) are evolutionary conserved from nematodes to man (Jacobsen and Iverfeldt in Cell Mol Life Sci 66:2299-2318, 2009) suggesting an important physiological function of these proteins. Human APP is a key factor in the pathogenesis of Alzheimer's Disease because its proteolytic processing results in the production of the neurotoxic Aβ-peptide, which accumulates in the amyloid plaques characteristic for this disease (Selkoe in Physiol Rev 81(2):741-766, 2001). However, the processing also leads to the production of several other fragments and the role of these products, as well as the function of the full-length protein is so far not well understood. The functional analysis of APP in vertebrates has been hampered by the fact that two close relatives, APLP1 and APLP2, exist and that knock-out mice for APP only show subtle defects. In contrast, invertebrates like Caenorhabditis elegans and Drosophila express only one APP-like protein but whereas a null mutation in the C. elegans APL-1 protein is lethal, flies lacking APPL (Amyloid Precursor Protein-like) are viable but show synaptic defects and behavioral abnormalities. Together with the analyses of flies that express APP proteins ectoptically or xenotopically, these studies show that APP proteins are involved in neuronal differentiation, neuritic outgrowth, and synapse formation. In addition, they play a role in long-term memory formation and maintaining brain integrity in adult flies.

Citing Articles

Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging.

Nithianandam V, Bukhari H, Leventhal M, Battaglia R, Dong X, Fraenkel E Nat Commun. 2023; 14(1):7034.

PMID: 37923712 PMC: 10624868. DOI: 10.1038/s41467-023-42822-1.

Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Models of Alzheimer's Disease.

Jalali D, Guevarra J, Martinez L, Hung L, Vonhoff F Int J Mol Sci. 2021; 22(13).

PMID: 34209883 PMC: 8269328. DOI: 10.3390/ijms22137022.

Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer's Disease Development.

Urban A, Pavlov K, Kamynina A, Okhrimenko I, Arseniev A, Bocharov E Molecules. 2021; 26(10).

PMID: 34068293 PMC: 8153327. DOI: 10.3390/molecules26102897.

Analysis of a cellular structure observed in the compound eyes of mutants and mutants.

Arimoto E, Kawashima Y, Choi T, Unagami M, Akiyama S, Tomizawa M Biol Open. 2019; 9(1).

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A Role for Amyloid Precursor Protein in Retrograde Trafficking of L1-Type Cell Adhesion Molecule Neuroglian.

Penserga T, Kudumala S, Poulos R, Godenschwege T Front Cell Neurosci. 2019; 13:322.

PMID: 31354437 PMC: 6640005. DOI: 10.3389/fncel.2019.00322.

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