Analysis of amyloid precursor protein function in Drosophila melanogaster

Marlène Cassar, Doris Kretzschmar

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

The Amyloid precursor protein (APP) has mainly been investigated in connection with its role in Alzheimer’s Disease (AD) due to its cleavage resulting in the production of the Aß peptides that accumulate in the plaques characteristic for this disease. However, APP is an evolutionary conserved protein that is not only found in humans but also in many other species, including Drosophila, suggesting an important physiological function. Besides Aß, several other fragments are produced by the cleavage of APP; large secreted fragments derived from the N-terminus and a small intracellular C-terminal fragment. Although these fragments have received much less attention than Aß, a picture about their function is finally emerging. In contrast to mammals, which express three APP family members, Drosophila expresses only one APP protein called APP-like or APPL. Therefore APPL functions can be studied in flies without the complication that other APP family members may have redundant functions. Flies lacking APPL are viable but show defects in neuronal outgrowth in the central and peripheral nervous system (PNS) in addition to synaptic changes. Furthermore, APPL has been connected with axonal transport functions. In the adult nervous system, APPL, and more specifically its secreted fragments, can protect neurons from degeneration. APPL cleavage also prevents glial death. Lastly, APPL was found to be involved in behavioral deficits and in regulating sleep/activity patterns. This review, will describe the role of APPL in neuronal development and maintenance and briefly touch on its emerging function in circadian rhythms while an accompanying review will focus on its role in learning and memory formation.

Original languageEnglish (US)
Article number61
JournalFrontiers in Molecular Neuroscience
Volume9
Issue numberJUL
DOIs
StatePublished - Jul 26 2016

Fingerprint

Amyloid beta-Protein Precursor
Drosophila melanogaster
Diptera
Drosophila
Nerve Degeneration
Axonal Transport
Peripheral Nervous System
Circadian Rhythm
Neuroglia
Nervous System
Mammals
Alzheimer Disease
Sleep
Proteins
Central Nervous System
Maintenance
Learning
Peptides

Keywords

  • Amyloid precursor proteins
  • Drosophila melanogaster
  • Neuronal outgrowth
  • Neuronal survival
  • Synaptogenesis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

Analysis of amyloid precursor protein function in Drosophila melanogaster. / Cassar, Marlène; Kretzschmar, Doris.

In: Frontiers in Molecular Neuroscience, Vol. 9, No. JUL, 61, 26.07.2016.

Research output: Contribution to journalReview article

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