scholarly journals Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Marcus O. W. Grimm ◽  
Sven Grösgen ◽  
Tatjana L. Rothhaar ◽  
Verena K. Burg ◽  
Benjamin Hundsdörfer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
De Novo ◽  
Physiological Function ◽  
Proteolytic Processing ◽  
Sphingolipid Metabolism ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Coa Transferase ◽  
Key Enzyme

Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipidde novosynthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic ADpostmortembrains, suggesting that SPT is involved in AD pathology.

scholarly journals Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2196
Author(s):  
Dingding Mo ◽  
Xinping Li ◽  
Carsten A. Raabe ◽  
Timofey S. Rozhdestvensky ◽  
Boris V. Skryabin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Cultured Cells ◽  
Alternative Pathway ◽  
Circular Rna ◽  
Proteolytic Processing ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Age Related

Alzheimer’s disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (Aβ) play a crucial role in the pathology of AD. In familial AD, Aβ are generated from the full-length amyloid beta precursor protein (APP) via dysregulated proteolytic processing; however, in the case of sporadic AD, the mechanism of Aβ biogenesis remains elusive. circRNAs are a class of transcripts preferentially expressed in brain. We identified a circRNA harboring the Aβ-coding region of the APP gene termed circAβ-a. This circular RNA was detected in the brains of AD patients and non-dementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circAβ-a is efficiently translated into a novel Aβ-containing Aβ175 polypeptide (19.2 KDa) in both cultured cells and human brain. Furthermore, Aβ175 was shown to be processed into Aβ peptides—a hallmark of AD. In summary, our analysis revealed an alternative pathway of Aβ biogenesis. Consequently, circAβ-a and its corresponding translation product could potentially represent novel therapeutic targets for AD treatment. Importantly, our data point to yet another evolutionary route for potentially increasing proteome complexity by generating additional polypeptide variants using back-splicing of primary transcripts that yield circular RNA templates.

scholarly journals The role of Aβ circRNA in Alzheimer’s disease: alternative mechanism of Aβ biogenesis from Aβ circRNA translation

2018 ◽  
Author(s):  
Dingding Mo ◽  
Xinping Li ◽  
Carsten A. Raabe ◽  
Timofey S. Rozhdestvensky ◽  
Boris V. Skryabin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Proteolytic Processing ◽  
Alternative Mechanism ◽  
Coding Region ◽  
Amyloid Beta Peptides ◽  
Aβ Peptides ◽  
Beta Peptides ◽  
Age Related

AbstractAlzheimer’s disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (Aβ) play a crucial role in the pathology of AD. In familial AD, Aβ is generated from the full-length amyloid precursor protein (APP) via dysregulated proteolytic processing. However, Aβ biogenesis in case of sporadic AD remains so far elusive. circRNAs are a class of transcripts, which are preferentially expressed in brain. Here, we identified a circRNA (circAβ-a) derived from the Aβ-coding region of the APP gene. circAβ-a is expressed in brains of AD and nondementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circAβ-a is efficiently translated into a novel Aβ-related Aβ175 protein in living cells. Importantly, Aβ175 was further processed to Aβ peptides, the hallmark of AD. In summary, our analysis revealed alternative route of Aβ biogenesis. circAβ-a and its corresponding protein might represent novel therapeutic targets for AD treatment.

scholarly journals Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease

2009 ◽  
Vol 5 (1) ◽  
pp. 18-29 ◽  
Author(s):  
Alex E. Roher ◽  
Chera L. Esh ◽  
Tyler A. Kokjohn ◽  
Eduardo M. Castaño ◽  
Gregory D. Van Vickle ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Plasma ◽  
Amyloid Beta ◽  
Amyloid Beta Peptides ◽  
Beta Peptides

Efficient Processing of Alzheimer's Disease Amyloid-Beta Peptides by Neuroectodermally Converted Mesenchymal Stem Cells

2010 ◽  
Vol 19 (5) ◽  
pp. 629-633 ◽  
Author(s):  
Hans-Jörg Habisch ◽  
Benjamin Schmid ◽  
Christine A.F. von Arnim ◽  
Albert C. Ludolph ◽  
Rolf Brenner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amyloid Beta ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Efficient Processing
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