Cited by 99Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchCellular transport and secretion

Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells

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Brunholz, Silke, Sisodia, Sangram, Lorenzo, Alfredo, Deyts, Carole, Kins, Stefan, Morfini, Gerardo·2012·Experimental Brain Research

Abstract

Over two decades have passed since the original discovery of amyloid precursor protein (APP). While physiological function(s) of APP still remain a matter of debate, consensus exists that the proteolytic processing of this protein represents a critical event in the life of neurons and that abnormalities in this process are instrumental in Alzheimer's disease (AD) pathogenesis. Specific molecular components involved in APP proteolysis have been identified, and their enzymatic activities characterized in great detail. As specific proteolytic fragments of APP are identified and novel physiological effects for these fragments are revealed, more obvious becomes our need to understand the spatial organization of APP proteolysis. Valuable insights on this process have been obtained through the study of non-neuronal cells. However, much less is known about the topology of APP processing in neuronal cells, which are characterized by their remarkably complex cellular architecture and extreme degree of polarization. In this review, we discuss published literature addressing various molecular mechanisms and components involved in the trafficking and subcellular distribution of APP and APP secretases in neurons. These include the relevant machinery involved in their sorting, the identity of membranous organelles in which APP is transported, and the molecular motor-based mechanisms involved in their translocation. We also review experimental evidence specifically addressing the processing of APP at the axonal compartment. Understanding neuron-specific mechanisms of APP processing would help illuminating the physiological roles of APP-derived proteolytic fragments and provide novel insights on AD pathogenesis.

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Crossref · 10.1007/s00221-011-2870-1

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115 of 115 references verified0 citation errors · 0 not checkable

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  • Movement of vesicles and endo-lysosomal compartments along axons is a key part of amyloid fibril formation and vesicle-mediated aggregation of Tau proteins.

    “The movement of vesicles and endo-lysosomal compartments along axons is a key part of amyloid fibril formation and vesicle-mediated aggregation of Tau proteins [7, 87].”

    From Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease (2023) · cites this paper as [7]

    The 'Axonal transport of APP' section describes movement of membrane-bounded organelles along axons, and 'Functional roles of APP metabolites in neurons' links axonally transported APP to Aβ deposited in amyloid plaques. The paper does not establish that this movement is a key part of amyloid fibril formation or vesicle-mediated Tau aggregation; it also does not identify the transported compartments specifically as endo-lysosomal. (LLM, conf=0.84)

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1 retracted

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1 of the 116 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Morfini GA Stenoien DL Brady ST Siegel G Albers RW Brady S Price D Axonal transport Basic neurochemistry 2006 485 502 Elsevier Academic Burlington 7th edn.
  2. Pigino G Morfini G Brady ST Siegel G Albers RW Brady S Price D Intracellular trafficking Basic neurochemistry 2006 139 164 Elsevier Academic Burlington 7th edn.
  3. Tsai M-Y Morfini G Szebenyi G Brady ST Modulation of kinesin-vesicle interactions by Hsc70: implications for regulation of fast axonal transport Molec Biol Cell 2000 11 2161 2173 10848636 PMC14910

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Authors
Brunholz, S., Sisodia, S., Lorenzo, A., Deyts, C., Kins, S., & Morfini, G.
Affiliations
  • University of Kaiserslautern (DE)
  • University of Chicago (US)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • University of Illinois Chicago (US)
Corresponding author
Morfini, Gerardo
Venue
Experimental Brain Research
Published
2011-09-30
Volume
217
Issue
3-4
Pages
353-364
ISSN
  • 0014-4819 (ISSN-L)
  • 1432-1106
OpenAlex
W1989258392
Cited by
92
References
116
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 9 · 2013: 7 · 2012: 8
FWCI
0.86
Type
journal article
Language
en
Open access
Locations
  • Experimental Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Brain Research Foundation
  • Eisai
  • National Institutes of Health
  • National Institute on Aging (R01AG021494)
  • National Institute of Neurological Disorders and Stroke (R01NS066942, R01 NS066942A)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
amyloid precursor protein, axonal transport, APP proteolysis, Alzheimer's disease, neuronal polarity, intracellular trafficking, motor proteins, axons, neurons
MeSH terms
Alzheimer Disease, Animals, Axonal Transport, Humans, Neurons, Protein Processing, Post-Translational, Subcellular Fractions, Amyloid beta-Protein Precursor, Protein Transport, Proteolysis

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