TGF-β1, regulation of Alzheimer amyloid precursor protein mRNA expression in a normal human astrocyte cell line: mRNA stabilization

Amara, Francis M.; Junaid, Asad; Clough, Richard R.; Liang, Binhua

doi:10.1016/s0169-328x(99)00158-8

Cited by 67 publications

(46 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro, an overexpression of APP mRNAs induced by TGF-␤1 has been reported previously in astrocytes or in astrocytoma cell line (46,47). Amara et al (47) have described an increased half-life of the APP transcripts induced by TGF-␤1.…”

Section: Tgf-␤1 Potentiates Amyloid-␤ Generationmentioning

confidence: 64%

Transforming Growth Factor-β1 Potentiates Amyloid-β Generation in Astrocytes and in Transgenic Mice

Lesné

Docagne

Gabriel

et al. 2003

Journal of Biological Chemistry

132

117

View full text Add to dashboard Cite

Accumulation of the amyloid-␤ peptide (A␤) in the brain is crucial for development of Alzheimer's disease. Expression of transforming growth factor-␤1 (TGF-␤1), an immunosuppressive cytokine, has been correlated in vivo with A␤ accumulation in transgenic mice and recently with A␤ clearance by activated microglia. Here, we demonstrate that TGF-␤1 drives the production of A␤40/42 by astrocytes leading to A␤ production in TGF-␤1 transgenic mice. First, TGF-␤1 induces the overexpression of the amyloid precursor protein (APP) in astrocytes but not in neurons, involving a highly conserved TGF-␤1-responsive element in the 5-untranslated region (؉54/؉74) of the APP promoter. Second, we demonstrated an increased release of soluble APP-␤ which led to TGF-␤1-induced A␤ generation in both murine and human astrocytes. These results demonstrate that TGF-␤1 potentiates A␤ production in human astrocytes and may enhance the formation of plaques burden in the brain of Alzheimer's disease patients.

show abstract

Section: Tgf-␤1 Potentiates Amyloid-␤ Generationmentioning

confidence: 64%

Transforming Growth Factor-β1 Potentiates Amyloid-β Generation in Astrocytes and in Transgenic Mice

Lesné

Docagne

Gabriel

et al. 2003

Journal of Biological Chemistry

132

117

View full text Add to dashboard Cite

show abstract

“…βAPP holoprotein synthesis by astrocytes can be stimulated by cytokines such as IL-1β, TNFα or TGF-β1 (Amara et al, 1999;Rogers et al, 1999) through regulation of gene transcription at the promoter level (Ge & Lahiri, 2002). Combinations of cytokines such as IL-1β or TNFα and IFN-γ are able to affect the metabolism of βAPP and to stimulate the production of Aβ40 and Aβ42 peptides (Blasko et al, 1999;Sastre et al, 2003).…”

Section: How Inflammatory Factors Might Affect the Processing Of βAppmentioning

confidence: 99%

How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes

et al. 2004

View full text Add to dashboard Cite

SummaryA huge amount of evidence has implicated amyloid beta (Aβ β β β ) peptides and other derivatives of the amyloid precursor protein (β β β β APP) as central to the pathogenesis of Alzheimer's disease (AD). It is also widely recognized that age is the most important risk factor for AD and that the innate immune system plays a role in the development of neurodegeneration. Little is known, however, about the molecular mechanisms that underlie age-related changes of innate immunity and how they affect brain pathology. Aging is characteristically accompanied by a shift within innate immunity towards a pro-inflammatory status. Pro-inflammatory mediators such as tumour necrosis factor-α α α α or interleukin-1β β β β can then in combination with interferon-γ γ γ γ be toxic on neurons and affect the metabolism of β β β β APP such that increased concentrations of amyloidogenic peptides are produced by neuronal cells as well as by astrocytes. A disturbed balance between the production and the degradation of Aβ β β β can trigger chronic inflammatory processes in microglial cells and astrocytes and thus initiate a vicious circle. This leads to a perpetuation of the disease.

show abstract

“…TGF␤1 enhanced the generation of A␤ in transgenic mice that constitutively overexpressed familial AD (FAD)-linked mutant APPs (21,47). TGF␤1 also was shown to enhance the expression of APP in vitro (1,12).…”

mentioning

confidence: 97%

Transforming Growth Factor β2 Is a Neuronal Death-Inducing Ligand for Amyloid-β Precursor Protein

Hashimoto¹,

Chiba²,

Yamada

et al. 2005

Molecular and Cellular Biology

View full text Add to dashboard Cite

APP, amyloid ␤ precursor protein, is linked to the onset of Alzheimer's disease (AD). We have here found that transforming growth factor ␤2 (TGF␤2), but not TGF␤1, binds to APP. The binding affinity of TGF␤2 to APP is lower than the binding affinity of TGF␤2 to the TGF␤ receptor. On binding to APP, TGF␤2 activates an APP-mediated death pathway via heterotrimeric G protein G o , c-Jun N-terminal kinase, NADPH oxidase, and caspase 3 and/or related caspases. Overall degrees of TGF␤2-induced death are larger in cells expressing a familial AD-related mutant APP than in those expressing wild-type APP. Consequently, superphysiological concentrations of TGF␤2 induce neuronal death in primary cortical neurons, whose one allele of the APP gene is knocked in with the V642I mutation. Combined with the finding indicated by several earlier reports that both neural and glial expression of TGF␤2 was upregulated in AD brains, it is speculated that TGF␤2 may contribute to the development of AD-related neuronal cell death.

show abstract

TGF-β1, regulation of Alzheimer amyloid precursor protein mRNA expression in a normal human astrocyte cell line: mRNA stabilization

Cited by 67 publications

References 28 publications

Transforming Growth Factor-β1 Potentiates Amyloid-β Generation in Astrocytes and in Transgenic Mice

Transforming Growth Factor-β1 Potentiates Amyloid-β Generation in Astrocytes and in Transgenic Mice

How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes

Transforming Growth Factor β2 Is a Neuronal Death-Inducing Ligand for Amyloid-β Precursor Protein

Contact Info

Product

Resources

About