Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Tangle Formation, Amyloid-β, and Microglia in Alzheimer’s Disease

Takata, Kazuyuki; Kitamura, Yoshihisa

doi:10.1254/jphs.11r10fm

Cited by 31 publications

(14 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[102][103][104] CFH expression is significantly downregulated in the degenerating brain and retina, suggesting that insufficient quantities of this RCA regulator lead to excessive activation of the innate immune response and proinflammatory signaling. [105][106][107][108][109][110][111][112][113][114][115][116][117] There are many shared pathologic characteristics of Alzheimer's disease (AD) and AMD, including decreases and/or dysfunction in CFH. 118 CFH inhibits alternative pathway activation both in plasma and on cell surfaces by promoting C3b proteolysis.…”

Section: Mirnas As Regulators Of the Inflammatory Process An Importamentioning

confidence: 99%

The role of epigenetics in age-related macular degeneration

Gemenetzi

Lotery

2014

Eye

View full text Add to dashboard Cite

It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcrip-

show abstract

Section: Mirnas As Regulators Of the Inflammatory Process An Importamentioning

confidence: 99%

The role of epigenetics in age-related macular degeneration

Gemenetzi

Lotery

2014

Eye

View full text Add to dashboard Cite

show abstract

“…AD pathology is characterized by the deposition of extracellular Aβ peptides and by intraneuronal accumulation of hyperphosphorylated and aggregated tau protein [1]. Beside the pathological accumulation of intraneuronal neurofibrillary tangles and extracellular Aβ deposits, neurodegeneration and neuroinflammation associated with microgliosis and astrogliosis are prevalent in AD brains.…”

Section: Introductionmentioning

confidence: 99%

Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice

Paris¹

2014

Brain Disord Ther

View full text Add to dashboard Cite

We have previously shown that the natural alkaloid anatabine displays some anti-inflammatory and Alzheimer amyloid (Aβ) lowering properties in the central nervous system associated with reduced STAT3 and NFkB activation. We investigated here the impact of a chronic oral treatment with anatabine in a model of tauopathy. We found that anatabine reduces the incidence of paralysis and abnormal hind limb extension reflex while improving rotarod performances in P301S mutant human Tau transgenic mice (Tg Tau P301S) suggesting that anatabine delays the disease progression in this model of tauopathy. Analyzes of brain and spinal cord homogenates reveal that anatabine reduces tau phosphorylation at multiple pertinent Alzheimer's disease (AD) epitopes and decreases the levels of pathological tau conformers/oligomers in both detergent soluble and insoluble fractions. Pathological tau species reduction induced by anatabine was accompanied by decreased Iba1 expression suggesting a diminution of microgliosis in the brain and spinal cord of Tg Tau P301S mice. In addition, we found that anatabine administration increases phosphorylation of the inhibitory residue (Ser9) of glycogen synthase kinase-3β, a primary tau kinase, associated with AD pathology, providing a possible mechanism for the observed reduction of tau phosphorylation. These data support further exploration of anatabine as a possible disease modifying agent for neurodegenerative tauopathies and, in particular AD, since anatabine also displays Aβ lowering properties.

show abstract

“…AD is related to the increase in amyloid b (Ab) level and hyperphosphorylated tau, along with loss of neurons and synapses (2). Therefore, it is likely that the dysfunction of AD brain does not arise from a single cause but from multiple causes.…”

Section: Introductionmentioning

confidence: 99%

Combination Effects of ZSET1446/ST101 With Memantine on Cognitive Function and Extracellular Acetylcholine in the Hippocampus

2013

View full text Add to dashboard Cite

Abstract. In the novel object recognition task, ZSET1446 (also coded as ST101) enhanced object recognition memory in mice and ameliorated cognitive impairment caused by scopolamine in rats. The enhancement induced by ZSET1446 in mice was abolished by injection of mechamylamine, a nonselective antagonist of nicotinic acetylcholine (ACh) receptors, or dihydro-berythroidine, a selective antagonist against the a4 subunit of nicotinic ACh receptors. These results suggest that the procognitive effect of ZSET146 is probably mediated by stimulation of nicotinic receptors. Memantine was also effective in these tests and concomitant administration of subeffective doses of ZSET1446 and memantine significantly ameliorated the cognitive performance in the novel object recognition task in both mice and rats. Moreover, oral administration of ZSET1446 or memantine increased the extracellular level of ACh in the hippocampus as compared with the control. Further, concomitant administration of subeffective doses of ZSET1446 and memantine significantly increased the extracellular level of ACh as compared with the group of ZSET1446 or memantine alone. These results suggest that these two compounds have a synergistic effect on the cognitive function possibly by synergistic increase in the extracellular level of ACh in the hippocampus, and that the combination therapy of these compounds might be effective in clinical settings.

show abstract

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Tangle Formation, Amyloid-β, and Microglia in Alzheimer’s Disease

Cited by 31 publications

References 60 publications

The role of epigenetics in age-related macular degeneration

The role of epigenetics in age-related macular degeneration

Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice

Combination Effects of ZSET1446/ST101 With Memantine on Cognitive Function and Extracellular Acetylcholine in the Hippocampus

Contact Info

Product

Resources

About