Probing the role of PPARγ in the regulation of late-onset Alzheimer’s disease-associated genes

Barrera, Julio; Subramanian, Shobana; Chiba‐Falek, Ornit

doi:10.1371/journal.pone.0196943

Cited by 18 publications

(12 citation statements)

References 43 publications

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“…PPARγ is expressed in brain tissue [ 18 ] and pioglitazone (a PPARγ agonist) may cross the blood-brain-barrier [ 19 ]. Knockdown of the PPARγ gene affects the expression of several genes associated with Alzheimer’s disease, suggesting that pioglitazone may regulate the transcription of genes related to Alzheimer’s disease and may potentially affect the risk of dementia [ 20 ]. Pioglitazone may alleviate insulin resistance, reduce Aβ synthesis, inhibit neuroinflammation and improve energy utilization and lipid metabolism in the brain [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis

Tseng

2018

JCM

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Background: The beneficial effect of pioglitazone on dementia requires confirmation. Methods: The database of Taiwan’s National Health Insurance was used to enroll a propensity score-matched-pair cohort of patients who had ever used pioglitazone and patients who had never used pioglitazone from Taiwanese patients with newly diagnosed diabetes mellitus during 1999–2008. The patients were to be alive on 1 January 2009 and were followed up for dementia until 31 December 2011. Hazard ratios were estimated using the Cox proportional hazards model. Results: There were 11,011 never users and 11,011 ever users of pioglitazone, with respective numbers of incident dementia of 123 and 91. The overall hazard ratio was 0.716 (95% confidence interval: 0.545–0.940) for ever users versus never users. The hazard ratios for the first (<11.0 months), second (11.0–19.6 months) and third (>19.6 months) tertiles of cumulative duration were 0.806 (0.544–1.193), 0.654 (0.430–0.994) and 0.694 (0.469–1.026), respectively. When cumulative duration was treated as a continuous variable, the hazard ratio was 0.987 (0.976–0.998). In subgroup analyses, the beneficial effect was mainly observed in patients who had not been treated with metformin. Among metformin ever users, the hazard ratio for dementia for pioglitazone ever users versus never users was 0.802 (0.580–1.109); and was 0.494 (0.284–0.857) among never users of metformin. No interaction between pioglitazone and major risk factors of dementia (i.e., stroke, hypoglycemia, head injury and Parkinson’s disease) was observed. Conclusions: Pioglitazone use is associated with a lower risk of dementia, especially when it is used in never users of metformin and has been used for more than 20 months.

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Section: Discussionmentioning

confidence: 99%

Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis

Tseng

2018

JCM

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“…PPAR␥ may act as a master regulator of the transcription of several genes involved in LOAD pathogenesis [84]. PPAR␥ agonists such as the glitazone, pioglitazone, prescribed for the treatment of type 2 diabetes, promote amyloid clearance in animal models of AD [85].…”

Section: Other Nuclear Receptor Agonistsmentioning

confidence: 99%

Is Alzheimer’s Disease a Liver Disease of the Brain?

Bassendine

Taylor-Robinson

Fertleman

et al. 2020

JAD

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Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer's disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid specialists on atherosclerosis. This article on AD focuses on the role of the liver and lipid homeostasis in the development of AD. Amyloid-␤ (A␤) deposits accumulate as plaques in the brain of an AD patient long before cognitive decline is evident. A␤ generation is a normal physiological process; the steady-state level of A␤ in the brain is determined by balance between A␤ production and its clearance. We present evidence suggesting that the liver is the origin of brain A␤ deposits and that it is involved in peripheral clearance of circulating A␤ in the blood. Hence the liver could be targeted to decrease A␤ production or increase peripheral clearance.

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“…Foi demonstrado que o PPARγ pode tanto ativar como reprimir a transcrição, em formas dependentes ou independentes de ligandos. Estudos utilizando modelos animais de Alzheimer sugeriram que o PPARγ exerce efeitos diretos e indiretos no metabolismo da proteína APP 42 .…”

Section: Resultsunclassified

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão

Câmara

2019

J. bras. psiquiatr.

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RESUMO Objetivo O artigo tem como objetivo determinar as famílias de receptores mais estudadas, envolvidas com a doença de Alzheimer, assim como determinar a região do sistema nervoso na qual mais tipos de receptores são expressos e quais funções dos receptores estão predominantemente associadas com a patologia em questão. O artigo busca mostrar os modelos e métodos mais utilizados nessas pesquisas, resumindo alguns achados e discutindo o impacto desses estudos no conhecimento científico. Métodos Esta revisão utilizou-se de uma metodologia sistemática (Prospero; ID 141957). Resultados Pode-se constatar que os receptores de transcrição nuclear foram os mais estudados. A maior parte desses receptores se expressa no córtex cerebral e hipocampo. Adicionalmente, a maioria das pesquisas avaliou os receptores relacionados com os efeitos benéficos na doença. A eliminação da proteína amiloide ou o bloqueio de vias relacionadas à síntese dessa proteína foram as principais funções desempenhadas por esses receptores. Por fim, as técnicas de imunoistoquímica e reação em cadeia de polimerase em tempo real (RT-PCR), respectivamente, foram as mais utilizadas, e os roedores consistiram no principal modelo de estudo. Conclusões Os receptores de transcrição nuclear, o córtex cerebral, o hipocampo, a micróglia e a proteína beta-amiloide mostraram importância na patogênese da doença de Alzheimer neste estudo.

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Probing the role of PPARγ in the regulation of late-onset Alzheimer’s disease-associated genes

Cited by 18 publications

References 43 publications

Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis

Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis

Is Alzheimer’s Disease a Liver Disease of the Brain?

Receptores neurais e a doença de Alzheimer: uma revisão sistemática da literatura sobre as famílias de receptores mais associadas a doença, suas funções e áreas de expressão

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