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The role of LAMP-2 ...
The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease
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- Boman, Andrea (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Janefjord, Camilla (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,CBD Solutions, Stockholm, Sweden
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- Halliday, Glenda (author)
- Neuroscience Research Australia and University of New South Wales, Sydney, Australia
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- Zetterberg, Henrik (author)
- Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden / UCL Institute of Neurology, Queen Square, London, United Kingdom
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- Blennow, Kaj (author)
- Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden
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- Garner, Brett (author)
- Illawarra Health and Medical Research Institute, Wollongong, Australia / School of Biological Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia
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- Miller, Bruce (author)
- Memory and Aging Center, University of California, San Francisco, United States
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- Saftig, Paul (author)
- Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany
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- Kågedal, Katarina (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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(creator_code:org_t)
- 2015
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
Close
- Dysfunction in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are implicated in the pathways in Alzheimer’s disease brain pathology. This dysfunction is mirrored in the cerebrospinal fluid where a specific subset of lysosomal network proteins are found at elevated levels, lysosomal associated membrane protein-2 (LAMP-2) being one of the identified lysosomal proteins. Here we report that hippocampus and frontal cortex in Alzheimer’s disease cases have increased mRNA and protein expression of LAMP-2, and thus these brain areas are likely involved in the increased LAMP-2 levels seen in cerebrospinal fluid from Alzheimer’s disease patients. The increased LAMP-2 levels correlated with increased levels of β-amyloid1-42 (Aβ1-42). Oligomeric Aβ1-42 caused an upregulation of intracellular LAMP-2 in neuroblastoma cells, but did not trigger the release of LAMP-2 to the extracellular milieu, indicating that other cell types or mechanisms are responsible for the LAMP-2 release seen in cerebrospinal fluid. Overexpression of LAMP-2 in neuroblastoma cells caused a trend of reduction of secreted Aβ1-42 and changed the processing pattern of the Aβ precursor protein. These results indicate that Aβ1-42 mediated increase of LAMP-2 expression can act as a regulator of Aβ generation and secretion. LAMP-2 overexpression did not change the cellular uptake of extracellularly added Aβ1-42, but caused a delayed clearance of Aβ1-42. Whether the prolonged intracellular localization of Aβ1-42 in LAMP-2 overexpressing cells can change the transmission or degradation of Aβ remains to be investigated.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Keyword
- AβPP processing
- Alzheimer’s disease
- β-amyloid
- autophagy
- LAMP-2
- lysosome
Publication and Content Type
- vet (subject category)
- ovr (subject category)
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