High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/220502 |
Resumo: | We have previously shown that the expression of nicotinamide N-methyltransferase (NNMT) is significantly increased in the brains of patients who have died of Parkinson’s disease (PD). In this study, we have compared the expression of NNMT in post-mortem medial temporal lobe, hippocampus and cerebellum of 10 Alzheimer’s disease (AD) and 9 non-disease control subjects using a combination of quantitative Western blotting, immunohistochemistry and dual-label confocal microscopy coupled with quantitative analysis of colocalisation. NNMT was detected as a single protein of 29 kDa in both AD and non-disease control brains, which was significantly increased in AD medial temporal lobe compared to non-disease controls (7.5-fold, P < 0.026). There was no significant difference in expression in the cerebellum (P = 0.91). NNMT expression in AD medial temporal lobe and hippocampus was present in cholinergic neurones with no glial localisation. Cell-type expression was identical in both non-disease control and AD tissues. These results are the first to show, in a proof-of-concept study using a small patient cohort, that NNMT protein expression is increased in the AD brain and is present in neurones which degenerate in AD. These results suggest that the elevation of NNMT may be a common feature of many neurodegenerative diseases. Confirmation of this overexpression using a larger AD patient cohort will drive the future development of NNMT-targetting therapeutics which may slow or stop the disease pathogenesis, in contrast to current therapies which solely address AD symptoms. |
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Kocinaj, AltinChaudhury, TabassumUddin, Mohammed S.Junaid, Rashad R.Ramsden, David B.Hondhamuni, GeshanthiKlamt, FabioParsons, LindaParsons, Richard B.2021-05-04T04:27:53Z20210893-7648http://hdl.handle.net/10183/220502001124672We have previously shown that the expression of nicotinamide N-methyltransferase (NNMT) is significantly increased in the brains of patients who have died of Parkinson’s disease (PD). In this study, we have compared the expression of NNMT in post-mortem medial temporal lobe, hippocampus and cerebellum of 10 Alzheimer’s disease (AD) and 9 non-disease control subjects using a combination of quantitative Western blotting, immunohistochemistry and dual-label confocal microscopy coupled with quantitative analysis of colocalisation. NNMT was detected as a single protein of 29 kDa in both AD and non-disease control brains, which was significantly increased in AD medial temporal lobe compared to non-disease controls (7.5-fold, P < 0.026). There was no significant difference in expression in the cerebellum (P = 0.91). NNMT expression in AD medial temporal lobe and hippocampus was present in cholinergic neurones with no glial localisation. Cell-type expression was identical in both non-disease control and AD tissues. These results are the first to show, in a proof-of-concept study using a small patient cohort, that NNMT protein expression is increased in the AD brain and is present in neurones which degenerate in AD. These results suggest that the elevation of NNMT may be a common feature of many neurodegenerative diseases. Confirmation of this overexpression using a larger AD patient cohort will drive the future development of NNMT-targetting therapeutics which may slow or stop the disease pathogenesis, in contrast to current therapies which solely address AD symptoms.application/pdfengMolecular neurobiology. Clifton. Vol. 58, no. 4 (Apr. 2021), p. 1769-1781Doença de AlzheimerNicotinamida N-metiltransferaseLobo temporalHipocampoAlzheimer’s diseaseNicotinamide N-methyltransferasePathogenic processOverexpressionTherapiesHomocysteineStress responseHigh expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s diseaseEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001124672.pdf.txt001124672.pdf.txtExtracted Texttext/plain59222http://www.lume.ufrgs.br/bitstream/10183/220502/2/001124672.pdf.txt2028b93669a6cc5ecb75865a80c1e283MD52ORIGINAL001124672.pdfTexto completo (inglês)application/pdf13466195http://www.lume.ufrgs.br/bitstream/10183/220502/1/001124672.pdfd564d908d031b837b4d19dddf32a2ef2MD5110183/2205022021-05-07 04:52:29.261379oai:www.lume.ufrgs.br:10183/220502Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-05-07T07:52:29Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
title |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
spellingShingle |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease Kocinaj, Altin Doença de Alzheimer Nicotinamida N-metiltransferase Lobo temporal Hipocampo Alzheimer’s disease Nicotinamide N-methyltransferase Pathogenic process Overexpression Therapies Homocysteine Stress response |
title_short |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
title_full |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
title_fullStr |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
title_full_unstemmed |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
title_sort |
High expression of nicotinamide N-methyltransferase in patients with sporadic Alzheimer’s disease |
author |
Kocinaj, Altin |
author_facet |
Kocinaj, Altin Chaudhury, Tabassum Uddin, Mohammed S. Junaid, Rashad R. Ramsden, David B. Hondhamuni, Geshanthi Klamt, Fabio Parsons, Linda Parsons, Richard B. |
author_role |
author |
author2 |
Chaudhury, Tabassum Uddin, Mohammed S. Junaid, Rashad R. Ramsden, David B. Hondhamuni, Geshanthi Klamt, Fabio Parsons, Linda Parsons, Richard B. |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Kocinaj, Altin Chaudhury, Tabassum Uddin, Mohammed S. Junaid, Rashad R. Ramsden, David B. Hondhamuni, Geshanthi Klamt, Fabio Parsons, Linda Parsons, Richard B. |
dc.subject.por.fl_str_mv |
Doença de Alzheimer Nicotinamida N-metiltransferase Lobo temporal Hipocampo |
topic |
Doença de Alzheimer Nicotinamida N-metiltransferase Lobo temporal Hipocampo Alzheimer’s disease Nicotinamide N-methyltransferase Pathogenic process Overexpression Therapies Homocysteine Stress response |
dc.subject.eng.fl_str_mv |
Alzheimer’s disease Nicotinamide N-methyltransferase Pathogenic process Overexpression Therapies Homocysteine Stress response |
description |
We have previously shown that the expression of nicotinamide N-methyltransferase (NNMT) is significantly increased in the brains of patients who have died of Parkinson’s disease (PD). In this study, we have compared the expression of NNMT in post-mortem medial temporal lobe, hippocampus and cerebellum of 10 Alzheimer’s disease (AD) and 9 non-disease control subjects using a combination of quantitative Western blotting, immunohistochemistry and dual-label confocal microscopy coupled with quantitative analysis of colocalisation. NNMT was detected as a single protein of 29 kDa in both AD and non-disease control brains, which was significantly increased in AD medial temporal lobe compared to non-disease controls (7.5-fold, P < 0.026). There was no significant difference in expression in the cerebellum (P = 0.91). NNMT expression in AD medial temporal lobe and hippocampus was present in cholinergic neurones with no glial localisation. Cell-type expression was identical in both non-disease control and AD tissues. These results are the first to show, in a proof-of-concept study using a small patient cohort, that NNMT protein expression is increased in the AD brain and is present in neurones which degenerate in AD. These results suggest that the elevation of NNMT may be a common feature of many neurodegenerative diseases. Confirmation of this overexpression using a larger AD patient cohort will drive the future development of NNMT-targetting therapeutics which may slow or stop the disease pathogenesis, in contrast to current therapies which solely address AD symptoms. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-05-04T04:27:53Z |
dc.date.issued.fl_str_mv |
2021 |
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Estrangeiro info:eu-repo/semantics/article |
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http://hdl.handle.net/10183/220502 |
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001124672 |
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http://hdl.handle.net/10183/220502 |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Molecular neurobiology. Clifton. Vol. 58, no. 4 (Apr. 2021), p. 1769-1781 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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