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Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know?
Alzheimer’s disease (AD) is the most common type of dementia, contributing to 60–80% of cases. It is a neurodegenerative disease that usually starts symptomless in the first two to three decades and then propagates into a long-term, irreversible disease, resulting in the progressive loss of memory,...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301342/ https://www.ncbi.nlm.nih.gov/pubmed/34356865 http://dx.doi.org/10.3390/biomedicines9070801 |
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author | Lin, Tong Tjernberg, Lars O. Schedin-Weiss, Sophia |
author_facet | Lin, Tong Tjernberg, Lars O. Schedin-Weiss, Sophia |
author_sort | Lin, Tong |
collection | PubMed |
description | Alzheimer’s disease (AD) is the most common type of dementia, contributing to 60–80% of cases. It is a neurodegenerative disease that usually starts symptomless in the first two to three decades and then propagates into a long-term, irreversible disease, resulting in the progressive loss of memory, reasoning, abstraction and language capabilities. It is a complex disease, involving a large number of entangled players, and there is no effective treatment to cure it or alter its progressive course. Therefore, a thorough understanding of the disease pathology and an early diagnosis are both necessary. AD has two significant pathological hallmarks: extracellular senile plaques composed of amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and the aggregation of Aβ, which starts in earlier stages, is usually claimed to be the primary cause of AD. Secretases that cleave Aβ precursor protein (APP) and produce neurotoxic Aβ reside in distinct organelles of the cell, and current concepts suggest that APP moves between distinct intracellular compartments. Obviously, APP transport and processing are intimately related processes that cannot be dissociated from each other, and, thus, how and where APP is transported determines its processing fate. In this review, we summarize critical mechanisms underlying neuronal APP transport, which we divide into separate parts: (1) secretory pathways and (2) endocytic and autophagic pathways. We also include two lipoprotein receptors that play essential roles in APP transport: sorting-related receptor with A-type repeats and sortilin. Moreover, we consider here some major disruptions in the neuronal transport of APP that contribute to AD physiology and pathology. Lastly, we discuss current methods and technical difficulties in the studies of APP transport. |
format | Online Article Text |
id | pubmed-8301342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83013422021-07-24 Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? Lin, Tong Tjernberg, Lars O. Schedin-Weiss, Sophia Biomedicines Review Alzheimer’s disease (AD) is the most common type of dementia, contributing to 60–80% of cases. It is a neurodegenerative disease that usually starts symptomless in the first two to three decades and then propagates into a long-term, irreversible disease, resulting in the progressive loss of memory, reasoning, abstraction and language capabilities. It is a complex disease, involving a large number of entangled players, and there is no effective treatment to cure it or alter its progressive course. Therefore, a thorough understanding of the disease pathology and an early diagnosis are both necessary. AD has two significant pathological hallmarks: extracellular senile plaques composed of amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and the aggregation of Aβ, which starts in earlier stages, is usually claimed to be the primary cause of AD. Secretases that cleave Aβ precursor protein (APP) and produce neurotoxic Aβ reside in distinct organelles of the cell, and current concepts suggest that APP moves between distinct intracellular compartments. Obviously, APP transport and processing are intimately related processes that cannot be dissociated from each other, and, thus, how and where APP is transported determines its processing fate. In this review, we summarize critical mechanisms underlying neuronal APP transport, which we divide into separate parts: (1) secretory pathways and (2) endocytic and autophagic pathways. We also include two lipoprotein receptors that play essential roles in APP transport: sorting-related receptor with A-type repeats and sortilin. Moreover, we consider here some major disruptions in the neuronal transport of APP that contribute to AD physiology and pathology. Lastly, we discuss current methods and technical difficulties in the studies of APP transport. MDPI 2021-07-10 /pmc/articles/PMC8301342/ /pubmed/34356865 http://dx.doi.org/10.3390/biomedicines9070801 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Lin, Tong Tjernberg, Lars O. Schedin-Weiss, Sophia Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? |
title | Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? |
title_full | Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? |
title_fullStr | Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? |
title_full_unstemmed | Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? |
title_short | Neuronal Trafficking of the Amyloid Precursor Protein—What Do We Really Know? |
title_sort | neuronal trafficking of the amyloid precursor protein—what do we really know? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301342/ https://www.ncbi.nlm.nih.gov/pubmed/34356865 http://dx.doi.org/10.3390/biomedicines9070801 |
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