Trafficking in neurons: Searching for new targets for Alzheimer's disease future therapies

Stefano Musardo, Claudia Saraceno, Silvia Pelucchi, Elena Marcello

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is the most common cause of dementia and no cure is available at the moment. As the disease progresses, patients become increasingly dependent, needing constant supervision and care. Prevention or delay of AD onset is among the most urgent moral, social, economic and scientific imperatives in industrialized countries. A better understanding of the pathogenic mechanisms leading to the disease and the consequent identification of new pharmacological targets are now a need. One of the most prominent molecular events occurring in AD patients' brains is the deposition of a peptide named amyloid-β (Aβ). Aβ derives from the concerted action of β-secretase, which mediates the amyloid precursor protein (APP) shedding at Aβ N-terminus, and γ-secretase, responsible for APP C-terminal stub cleavage. The production of Aβ can be prevented by the cleavage of ADAM10 on APP. In regard of AD pathogenesis, it is notable that neurons are the cell type affected in AD and that APP and the secretases are all integral transmembrane proteins, and so they are dynamically sorted in neurons. Therefore, neuronal sorting mechanisms responsible for APP and the secretases colocalization in the same membranous compartment play important roles in the regulation of Aβ production. In light of these considerations, this review provides an overview on the actual knowledge of the trafficking mechanisms involved in the regulation of APP and secretases localization, paying particular attention to the specific neuronal setting.

Original languageEnglish
Pages (from-to)84-106
Number of pages23
JournalEuropean Journal of Pharmacology
Volume719
Issue number1-3
DOIs
Publication statusPublished - 2013

Fingerprint

Amyloid Precursor Protein Secretases
Alzheimer Disease
Neurons
Amyloid beta-Protein Precursor
Amyloid
Therapeutics
Protein C
Developed Countries
Dementia
Economics
Pharmacology
Peptides
Brain
Proteins

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Amyloid precursor protein
  • Secretase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Trafficking in neurons : Searching for new targets for Alzheimer's disease future therapies. / Musardo, Stefano; Saraceno, Claudia; Pelucchi, Silvia; Marcello, Elena.

In: European Journal of Pharmacology, Vol. 719, No. 1-3, 2013, p. 84-106.

Research output: Contribution to journalReview article

Musardo, Stefano ; Saraceno, Claudia ; Pelucchi, Silvia ; Marcello, Elena. / Trafficking in neurons : Searching for new targets for Alzheimer's disease future therapies. In: European Journal of Pharmacology. 2013 ; Vol. 719, No. 1-3. pp. 84-106.
@article{15248d23f68a4e09a2cf6072840cd649,
title = "Trafficking in neurons: Searching for new targets for Alzheimer's disease future therapies",
abstract = "Alzheimer's disease (AD) is the most common cause of dementia and no cure is available at the moment. As the disease progresses, patients become increasingly dependent, needing constant supervision and care. Prevention or delay of AD onset is among the most urgent moral, social, economic and scientific imperatives in industrialized countries. A better understanding of the pathogenic mechanisms leading to the disease and the consequent identification of new pharmacological targets are now a need. One of the most prominent molecular events occurring in AD patients' brains is the deposition of a peptide named amyloid-β (Aβ). Aβ derives from the concerted action of β-secretase, which mediates the amyloid precursor protein (APP) shedding at Aβ N-terminus, and γ-secretase, responsible for APP C-terminal stub cleavage. The production of Aβ can be prevented by the cleavage of ADAM10 on APP. In regard of AD pathogenesis, it is notable that neurons are the cell type affected in AD and that APP and the secretases are all integral transmembrane proteins, and so they are dynamically sorted in neurons. Therefore, neuronal sorting mechanisms responsible for APP and the secretases colocalization in the same membranous compartment play important roles in the regulation of Aβ production. In light of these considerations, this review provides an overview on the actual knowledge of the trafficking mechanisms involved in the regulation of APP and secretases localization, paying particular attention to the specific neuronal setting.",
keywords = "Alzheimer's disease, Amyloid β, Amyloid precursor protein, Secretase",
author = "Stefano Musardo and Claudia Saraceno and Silvia Pelucchi and Elena Marcello",
year = "2013",
doi = "10.1016/j.ejphar.2013.07.019",
language = "English",
volume = "719",
pages = "84--106",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Trafficking in neurons

T2 - Searching for new targets for Alzheimer's disease future therapies

AU - Musardo, Stefano

AU - Saraceno, Claudia

AU - Pelucchi, Silvia

AU - Marcello, Elena

PY - 2013

Y1 - 2013

N2 - Alzheimer's disease (AD) is the most common cause of dementia and no cure is available at the moment. As the disease progresses, patients become increasingly dependent, needing constant supervision and care. Prevention or delay of AD onset is among the most urgent moral, social, economic and scientific imperatives in industrialized countries. A better understanding of the pathogenic mechanisms leading to the disease and the consequent identification of new pharmacological targets are now a need. One of the most prominent molecular events occurring in AD patients' brains is the deposition of a peptide named amyloid-β (Aβ). Aβ derives from the concerted action of β-secretase, which mediates the amyloid precursor protein (APP) shedding at Aβ N-terminus, and γ-secretase, responsible for APP C-terminal stub cleavage. The production of Aβ can be prevented by the cleavage of ADAM10 on APP. In regard of AD pathogenesis, it is notable that neurons are the cell type affected in AD and that APP and the secretases are all integral transmembrane proteins, and so they are dynamically sorted in neurons. Therefore, neuronal sorting mechanisms responsible for APP and the secretases colocalization in the same membranous compartment play important roles in the regulation of Aβ production. In light of these considerations, this review provides an overview on the actual knowledge of the trafficking mechanisms involved in the regulation of APP and secretases localization, paying particular attention to the specific neuronal setting.

AB - Alzheimer's disease (AD) is the most common cause of dementia and no cure is available at the moment. As the disease progresses, patients become increasingly dependent, needing constant supervision and care. Prevention or delay of AD onset is among the most urgent moral, social, economic and scientific imperatives in industrialized countries. A better understanding of the pathogenic mechanisms leading to the disease and the consequent identification of new pharmacological targets are now a need. One of the most prominent molecular events occurring in AD patients' brains is the deposition of a peptide named amyloid-β (Aβ). Aβ derives from the concerted action of β-secretase, which mediates the amyloid precursor protein (APP) shedding at Aβ N-terminus, and γ-secretase, responsible for APP C-terminal stub cleavage. The production of Aβ can be prevented by the cleavage of ADAM10 on APP. In regard of AD pathogenesis, it is notable that neurons are the cell type affected in AD and that APP and the secretases are all integral transmembrane proteins, and so they are dynamically sorted in neurons. Therefore, neuronal sorting mechanisms responsible for APP and the secretases colocalization in the same membranous compartment play important roles in the regulation of Aβ production. In light of these considerations, this review provides an overview on the actual knowledge of the trafficking mechanisms involved in the regulation of APP and secretases localization, paying particular attention to the specific neuronal setting.

KW - Alzheimer's disease

KW - Amyloid β

KW - Amyloid precursor protein

KW - Secretase

UR - http://www.scopus.com/inward/record.url?scp=84888289680&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888289680&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2013.07.019

DO - 10.1016/j.ejphar.2013.07.019

M3 - Review article

C2 - 23891967

AN - SCOPUS:84888289680

VL - 719

SP - 84

EP - 106

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -