HSP70の抗アルツハイマー病作用と30の活性方法 

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Hsp70とアルツハイマー病

関連記事

ヒートショックプロテイン(分子シャペロン)

HSP70の抗アルツハイマー病作用 30の活性方法

神経変性疾患の治療標的HSP90 16のHSP90阻害剤

ミトコンドリア熱ショックタンパク質 HSP60

低分子量HSP(スモールヒートショックプロテイン)

概要

HSP70は、ストレスから細胞を保護するために、さまざまなストレスに反応してタンパク質の凝集を防いだり折りたたみ機能を改善するタンパク質。

HSP70ファミリーは、主にタンパク質が生体膜を透過する際に穴を通りやすくするためにアンフォールディング(折りたたみの解除)に関与する。

HSP70シャペロンは、核、細胞質、ミトコンドリア、小胞体を含むほとんどの細胞コンパートメントに見られる。

The Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases - PubMed
The accumulation of misfolded proteins in the human brain is one of the critical features of many neurodegenerative diseases, including Alzheimer's disease (AD)
さまざまなストレスによって増加するHSP70

Hsp70ファミリーメンバーは熱以外にも、虚血、重金属、栄養欠乏、水分不足、紫外線、感染、炎症、有機物や酸化剤など毒素への曝露等多くのストレス要因で増加する。

特にヒ素、カドミウム、銅、水銀などの重金属によって非常に強くアップレギュレーションを示す。

The human HSP70 family of chaperones: where do we stand?
The 70-kDa heat shock protein (HSP70) family of molecular chaperones represents one of the most ubiquitous classes of chaperones and is highly conserved in all
HSP70ファミリーのアイソフォーム

Hsp70ファミリーは17個の遺伝子によってコードされており、ストレスによって引き起こされる誘導型と、ストレスがなくても存在する常時型が存在する。

・HSC70(HSP73/HSPA8)安静時にも発現

・HSP72(HSPA1A/HSPA1B)熱や酸化ストレスなどにより発現する誘導型

HSP70-2 脳と精巣で高度に存在し、腫瘍において過剰発現が認められる。

HSP70-5 神経変性疾患において関連性がある可能性。

mtHsp70(GRP75) ミトコンドリアHSP

HSP40 HSP70のコシャペロン(補助因子)として働く。

アンフォールディングシャペロン

HSP70はタンパク質の折りたたみと折りたたみの解除の両方を行うが、本質的にはタンパク質のアンフォールディングマシンとして機能する。

Hsc70は、ATPに依存したメカニズムによって(HSP90とは異なる)HSPと相互作用する(クライアント)タンパク質の折りたたみをサポートし、フォールディングされていないタンパク質の凝集を防ぐ。

The HSP70 family and cancer
The HSP70 family of heat shock proteins consists of molecular chaperones of approximately 70kDa in size that serve critical roles in protein homeostasis. These

Hsp70は補助因子であるコシャペロンHsp40と結合し、さまざまな細胞区画でHsp90と協同で作用する。

Cytosolic Hsp70 and Hsp40 chaperones enable the biogenesis of mitochondrial β-barrel proteins - PubMed
Mitochondrial β-barrel proteins are encoded in the nucleus, translated by cytosolic ribosomes, and then imported into the organelle. Recently, a detailed unders

Hsc70

Hsc70とHsp70

ヒトHsc70とヒトHsp70には、85%の相同性がある。

Hsp70とHsc70は同じ細胞の役割を担っていると長い間想定してきたが、現在ではこの仮定は不完全であることが判明している。

Hsc70は、標準的な熱ショックタンパク質とは異なり、熱ストレスのない通常の条件下でも発現しシャペロンとしての機能を実行する。

Hscは、タンパク質のユビキチン化や分解などの通常の細胞プロセスに関連する機能を実行する。

Biochemical and Proteomic Analysis of Ubiquitination of Hsc70 and Hsp70 by the E3 Ligase CHIP - PubMed
The E3 ubiquitin ligase CHIP is involved in protein triage, serving as a co-chaperone for refolding as well as catalyzing ubiquitination of substrates. CHIP fun

 

HSP70と疾患

アポトーシスへの抵抗性

アポトーシスを誘導する薬剤に対して、Hsp70レベルのダウンレギュレーションは感受性を高め、反対にHsp70の過剰発現はアポトーシス誘導剤に対する抵抗性を決定することができる。

Downregulation of Hsp70 inhibits apoptosis induced by sialic acid-binding lectin (leczyme) - PubMed
Heat shock proteins (Hsps) are molecular chaperones that maintain homeostasis of organisms. In regards to the Hsps, many studies have investigated the structure
Silencing of Hsp70 intensifies 6-OHDA-induced apoptosis and Hsp90 upregulation in PC12 cells - PubMed
By the current study, we tried to find out the interactive mechanisms enrolled by Hsp70 and Hsp90 following the 6-hydroxydopamine (6-OHDA)-induced oxidative str
腫瘍の促進

Hsp70レベルはさまざまな種類の腫瘍で増加し、乳がんおよび子宮内膜がんの予後不良と関連している。Hsp70は乳癌の細胞増殖と化学療法(抗がん剤)に対する耐性を増加させる。

Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy - PubMed
Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy
Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer - PubMed
HSP70-2 is over expressed in breast cancer patients and was involved in malignant properties of breast cancer. This suggests HSP70-2 may be potential candidate
The HSP70 family and cancer - PubMed
The HSP70 family of heat shock proteins consists of molecular chaperones of approximately 70kDa in size that serve critical roles in protein homeostasis. These
自然免疫応答の活性

Hsp70は、自然免疫と適応免疫の両方を刺激することにより、免疫応答の活性化を引き起こすことができる。

Hsp70は、エキソソーム経路を含む異常なタンパク質分泌経路を介して、さまざまなタイプの細胞から積極的に分泌される。

Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72 - PubMed
IFN-gamma exhibits differential effects depending on the target and can induce cellular activation and enhance survival or mediate cell death via activation of
Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells - PubMed
Detergent-soluble membrane vesicles are actively released by human pancreas (Colo-/Colo+) and colon (CX-/CX+) carcinoma sublines, differing in their capacity to
糖尿病・インスリン抵抗性

HSP70は加齢に伴うサルのインスリン変化と関連しており、高いHSP70は健康な高齢者のインスリン抵抗性に対して保護効果をもつ。

Muscle heat shock protein 70 predicts insulin resistance with aging - PubMed
Heat shock protein 70 (HSP70) protects cells from accumulating damaged proteins and age-related functional decline. We studied plasma and skeletal muscle (SkM)
Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance - PubMed
Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications, and stress proteins have been shown to protect organisms in vit
Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism - PubMed
To examine whether genes associated with cellular defense against oxidative stress are associated with insulin sensitivity, patients with type 2 diabetes (n = 7
Chaperoning to the metabolic party: The emerging therapeutic role of heat-shock proteins in obesity and type 2 diabetes
From their initial, accidental discovery 50 years ago, the highly conserved Heat Shock Proteins (HSPs) continue to exhibit fundamental roles in the protection o

HSP72は、肥満によるインスリン抵抗性を防ぐ

HSP72 protects against obesity-induced insulin resistance - PubMed
Patients with type 2 diabetes have reduced gene expression of heat shock protein (HSP) 72, which correlates with reduced insulin sensitivity. Heat therapy, whic
抗酸化活性
Heat shock protein 70 regulates cellular redox status by modulating glutathione-related enzyme activities - PubMed
Heat shock protein (Hsp) 70 has been reported to protect various cells and tissues from ischemic damage. However, the molecular mechanisms of the protection are

アルツハイマー病

小胞体・HSP70-5

パーキンソン病、アルツハイマー病、などの神経変性障害では小胞体に常駐するHsp70-5レベルが変化していることが多くの証拠によって示されている。

これらの障害は小胞体ストレスによるUPRの活性化が関連していると考えられている。

Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice - PubMed
The endoplasmic reticulum (ER) stress results from disrupted protein folding triggered by protein mutation or oxidation, reduced proteasome activity, and altere
Induction of endoplasmic reticulum stress genes, BiP and chop, in genetic and environmental models of retinal degeneration - PubMed
Our study reveals surprising increases in BiP and to a lesser degree Chop in retinal degenerations arising from diverse causes. We propose that manipulation of
HSP70-5の機能喪失

HSP70-5の機能喪失が、パーキンソン病、アルツハイマー病、および加齢黄斑変性を含む多くの加齢性神経変性障害の素因となる可能性があるかどうか提起されている。

The effect of aging on the chaperone concentrations in the hepatic, endoplasmic reticulum of male rats: the possible role of protein misfolding due to the loss of chaperones in the decline in physiological function seen with age - PubMed
The endoplasmic reticulum (ER) chaperones are highly conserved proteins that catalyze the posttranslational processing of all secretory and membrane proteins. O
Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers - PubMed
The endoplasmic reticulum (ER) is a target for endogenously generated reactive oxygen species (ROS) during aging. We have previously shown that the ER chaperone
アミロイドβ・オリゴマーの阻害

マウスのHSP70の過剰発現は、アミロイドβオリゴマーの阻害とアミロイドβの食作用により細胞保護効果を発揮する。

Suppression of Alzheimer's disease-related phenotypes by expression of heat shock protein 70 in mice - PubMed
Amyloid-β peptide (Aβ) plays an important role in the pathogenesis of Alzheimer's disease (AD). Aβ is generated by proteolysis of β-amyloid precursor protein (A
アミロイドオリゴマー凝集阻害

自然に折りたたまれたアミロイドオリゴマーは、シャペロンタンパク質HSP70によって凝集を阻害するように進化上できているようである。

しかし、ヒトの長寿命化などいくつかの条件によって生じたアミロイドオリゴマーの多種多様性によって、そのタンパク質凝集を抑制するための生体システムから逸脱してしまっているのかもしれない。

Amyloid Oligomer Conformation in a Group of Natively Folded Proteins
Recent in vitro and in vivo studies suggest that destabilized proteins with defective folding induce aggregation and toxicity in protein-misfolding diseases. On
プロテアソームを介したアミロイドとタウの分解

Hsp70はプロテアソーム系を介してタウおよびアミロイドβオリゴマーを分解する可能性がある。

Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin - PubMed
The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thoug

HSPがアミロイドβ凝集を阻害するメカニズムは2つ提案されている。

1.シャペロンはミスフォールディングされたアミロイドをATPに依存しない方法で結合し、凝集を防ぐ。

2.シャペロンはATP依存的にアミロイドβと結合し、アミロイドβの立体構造を凝集しにくいいものに変化させる。

Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro - PubMed
Alzheimer disease is a neurological disorder that is characterized by the presence of fibrils and oligomers composed of the amyloid beta (Abeta) peptide. In mod
タウの分解

Hsp70を含むシャペロンタンパク質は、異常タウに直接結合し、分解と脱リン酸化を促進することで濃度を低下させることができる。

図2

The Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases - PubMed
The accumulation of misfolded proteins in the human brain is one of the critical features of many neurodegenerative diseases, including Alzheimer's disease (AD)
IDE・TGF-β1活性によるアミロイドβクリアランス

HSP70はIDE発現、TGF-β1刺激を介してアミロイドβクリアランスを促進

抗アポトーシス

HSP70はApaf-1カスパーゼ依存性およびAIFカスパーゼ非依存性経路の両方を調節することでアポトーシスを減弱させ、神経細胞死を抑制することを示す。

ALS

二重盲検無作為化プラセボ対照試験ALS患者へのアリモクロモール(HSP誘導剤)投与

Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis - Full Text View - ClinicalTrials.gov
Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis - Full Text View.

アリモクロモール200mg tid 12ヶ月の投与は、安全性かつ忍容性が高い。プラセボ郡と統計的に有意な違いは示さなかったが、臨床的には意味のある差が見いだせた。

画像、イラストなどを保持する外部ファイル。オブジェクト名はNEUROLOGY2017818120FF2.jpgです。

Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS
To examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding

Hsc70とHsp72の異なるタウへの作用

HSP70タンパク質はタウ分解の加速と減速の両方を引き起こすとも考えられている。

Hsc70とHsp72には、相対的な発現レベル、タウの親和性、およびC末端相互作用ドメインによって駆動されるタウに対する反対の効果があることがわかった。

HSP72は熱ショック同族の70(HSC70)と比較してタウに対する親和性が高いことが示されている。ただし、脳組織ではHSC70がHSP72よりも豊富。

Hsc70およびHsp72のC末端のダイナミクスがタウの分解の加速または減速するために不可欠であることを示唆している。

アルツハイマー病ではHsp72レベルが誘導されないこともわかった。

Hsp72レベルは、疾患初期に上昇する可能性があるが、その後、慢性的なタンパク質毒性ストレスのために、時間とともに減衰してベースラインレベルに戻る。

したがって、HSC70の増加はタウのクリアランスが遅くなる可能性が高くなる。

Imbalance of Hsp70 family variants fosters tau accumulation - PubMed
Dysfunctional tau accumulation is a major contributing factor in tauopathies, and the heat-shock protein 70 (Hsp70) seems to play an important role in this accu

HSP70の治療戦略

HSP70を内因的に誘導
  • エストロゲンがストレス条件下でHSP70の発現を促進する可能性がある。
  • GGA(テプレノン)
  • クルクミン
  • セラストロール
HSP70を外因的に投与

Hsp70を鼻腔から投与

HSP70のATPアーゼ利用を阻害

メチレンブルーはATPアーゼの阻害剤

Heat Shock Protein 70 in Alzheimer's Disease
Alzheimer's disease (AD) is the most common neurodegenerative disease that caused dementia which has no effective treatment. Growing evidence has demonstrated t
HSP70変異体を制御する

HSP72を増やしHSC70を阻害する。

※HSP70変異体はタウクリアランスを促進する一方、構造的に不安定なタウを温存し病原性を促進する。

HSP72の促進・HSP70の阻害

Hsp70ファミリー変異体の不均衡は、タウの蓄積を促進する。

タウの存在下ではHsp70ではなくHsp72が、タウのユビキチン化を促進する。

Hsp72発現を促進しHsc70を阻害することで、タウオパチー治療に寄与しうる。

Imbalance of Hsp70 family variants fosters tau accumulation - PubMed
Dysfunctional tau accumulation is a major contributing factor in tauopathies, and the heat-shock protein 70 (Hsp70) seems to play an important role in this accu

HSP70の阻害要因

肥満

肥満は加熱に対するHSP70の応答障害と関連する。

The effect of passive heating on heat shock protein 70 and interleukin-6: A possible treatment tool for metabolic diseases?
Increasing physical activity remains the most widely publicized way of improving health and wellbeing. However, in populations that benefit most from exercise (
高脂肪食

高脂肪食による肥満はHSP発現を低下させる可能性があり、HSP発現を増加させることは、高脂肪食による肥満によって引き起こされる細胞損傷を緩和し、インスリン感受性を高目、炎症を軽減する可能性がある。

Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review
Interest in the heat shock proteins (HSPs), as a natural physiological toolkit of living organisms, has ranged from their chaperone function in nascent proteins
低い有酸素運動能力
Deficiency in the Heat Stress Response Could Underlie Susceptibility to Metabolic Disease - PubMed
Heat treatment (HT) effectively prevents insulin resistance and glucose intolerance in rats fed a high-fat diet (HFD). The positive metabolic actions of heat sh
銅欠乏
Dietary copper deficiency reduces heat shock protein expression in cardiovascular tissues - PubMed
Dietary copper deficiency impairs cardiovascular function by depression of catecholamine metabolism, and alteration of the structure and function of cardiac mit
ケルセチン
Quercetin mitigates lead acetate-induced behavioral and histological alterations via suppression of oxidative stress, Hsp-70, Bak and upregulation of Bcl-2 - PubMed
Lead toxicity is of major health concern due to its persistence in environment that induces cognitive impairment and neuronal degeneration. The present study wa

HSP70の活性

ライフスタイル

熱誘導によるHsp70シャペロン増加は、細胞内の亜鉛利用能と強く相関

Zinc supplementation boosts the stress response in the elderly: Hsp70 status is linked to zinc availability in peripheral lymphocytes - PubMed
Chaperones and zinc are indispensable for proper immune function. All the zinc status, the immune function and the stress response decline during aging. Here we
Heat Stress and Cardiovascular, Hormonal, and Heat Shock Proteins in Humans
Conditions such as osteoarthritis, obesity, and spinal cord injury limit the ability of patients to exercise, preventing them from experiencing many well-docume
サウナ

サウナなどの急性的な加熱を利用したHSP70の増加による健康享受は、運動を行わない個人の代替的ツールとなるかもしれない。

The effect of passive heating on heat shock protein 70 and interleukin-6: A possible treatment tool for metabolic diseases?
Increasing physical activity remains the most widely publicized way of improving health and wellbeing. However, in populations that benefit most from exercise (
The effect of passive heating on heat shock protein 70 and interleukin-6: A possible treatment tool for metabolic diseases?
Increasing physical activity remains the most widely publicized way of improving health and wellbeing. However, in populations that benefit most from exercise (
マイルド加温療法
HSPとは?
ヒートショックプロテインを増やして健康に。そのヒートショックプロテインについて、詳しく説明しています。
運動
Role of heat shock proteins in the exercise response - PubMed
Heat shock proteins (HSP) are a characteristic set of highly conserved proteins that are synthesized shortly after the organism is exposed to external stress, i
Heat Shock Proteins and Exercise in Humans
Heat shock proteins (HSPs) are increasingly seen as important players in the response of our biochemistry to stresses and damage. HSPs are fundamentally chapero
睡眠

睡眠不足は、ヒートショックプロテインの著しい減少にむすびつく可能性がある。

Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep - PubMed
Although sleep is thought to be restorative from prior wakeful activities, it is not clear what is being restored. To determine whether the synthesis of macromo
食事制限
Effect of age and dietary restriction on expression of heat shock protein 70 in rat alveolar macrophages - PubMed
Dietary restriction (DR) is the only effective experimental manipulation known to retard aging in rodents, and this manipulation has been shown to alter a varie
カロリー制限
Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans - PubMed
The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating th

食事

スルフォラファン
HSF1-Dependent Upregulation of Hsp70 by Sulfhydryl-Reactive Inducers of the KEAP1/NRF2/ARE Pathway
The KEAP1/NRF2/ARE pathway and the heat shock response are inducible cytoprotective systems regulated by transcription factors NRF2 and HSF1, respectively. We r
ブルーベリー
Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection - PubMed
Dietary supplementation with antioxidant rich foods can decrease the level of oxidative stress in brain regions and can ameliorate age-related deficits in neuro
オリーブオイル
Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil: A new family of gerosuppressant agents
Aging can be viewed as a quasi-programmed phenomenon driven by the overactivation of the nutrient-sensing mTOR gerogene. mTOR-driven aging can be triggered or a
牛の初乳
The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes - PubMed
Heavy exercise causes gut symptoms and, in extreme cases, "heat stroke" partially due to increased intestinal permeability of luminal toxins. We examined bovine
ニンニク(アリシン)
Allicin protects traumatic spinal cord injury through regulating the HSP70/Akt/iNOS pathway in mice - PubMed
Allicin is a major component of garlic, extracted as an oily liquid. The present study was designed to investigate the beneficial effects of allicin on traumati
チアシード
Chia (Salvia hispanica L.) enhances HSP, PGC-1α expressions and improves glucose tolerance in diet-induced obese rats - PubMed
Chia oil restored the antioxidant system and induced the expression of a higher number of proteins than chia seed. The present study demonstrated new properties
ホエイプロテイン
Bioactivity of food peptides: biological response of rats to bovine milk whey peptides following acute exercise - PubMed
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioacti
Functional effects of milk bioactive peptides on skeletal muscle of rats
Whey protein hydrolysate (WPH) intake has shown to enhance heat shock proteins (HSPs). The presence of bioactive peptides has been suggested to affect…
プロバイオティクス(ラクトバチルスGG)
Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells - PubMed
Conditioned media from the probiotic Lactobacillus GG (LGG-CM) induce heat shock protein (Hsp) expression in intestinal epithelial cells. LGG-CM induces both Hs

ハーブ

クルクミン

クルクミンは、Fyn抑制によるHSP90阻害を介してその神経保護効果の一部を発揮している可能性がある。

Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin - PubMed
The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thoug
Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice - PubMed
The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic imp
ペオニフロリン(芍薬)

培養した哺乳動物細胞においてHsp70、Hsp40、Hsp27を誘導

Paeoniflorin, a novel heat shock protein-inducing compound - PubMed
Heat shock proteins (HSPs) are induced by various physical, chemical, and biological stresses. HSPs are known to function as molecular chaperones, and they not
レスベラトロール

マウスへのレスベラトロール注入は、Hsp25およびHsp70を上昇させ、熱ショック因子1(HSF1)のアセチル化を減少させた。

Resveratrol upregulated heat shock proteins and extended the survival of G93A-SOD1 mice - PubMed
In the present study, we investigated whether resveratrol, a SIRT1 activator, can suppress the motor neuron degeneration in a transgenic mouse model of amyotrop
ヤマブシタケ

ヘリシウム・エリナセウス(ヤマブシタケ)がラットのHsp70をアップレギュレーションさせ胃粘膜を保護した。

Gastroprotective Effects of Lion’s Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats
Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Spr
イチョウ葉抽出物
ライオンズメーン(ヤマブシタケ)
Gastroprotective Effects of Lion’s Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats
Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Spr
セラストロール
Induction of heat shock proteins in cerebral cortical cultures by celastrol - PubMed
Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) are 'protein misfolding disorders' of the mature nervous system that are charac
緑茶エキス
(-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78 - PubMed
Many beneficial properties have been attributed to (-)-epigallocatechin gallate (EGCG), including chemopreventive, anticarcinogenic, and antioxidant actions. In
プロポリス
Protective effects of propolis on methotrexate-induced testis injury in rat - PubMed
Propolis is an adhesive substance which is collected and used by honeybees. Propolis is a potent antioxidant and a free radical scavenger. This study was design
ミリセチン

ATPase活性を最大で75%抑制

Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism - PubMed
DnaK is a molecular chaperone responsible for multiple aspects of bacterial proteostasis. The intrinsically slow ATPase activity of DnaK is stimulated by its co

栄養化合物・ホルモン

グルタミン

グルタミン投与はHsp70発現の誘導に部分的に関与する。ラット

Glutamine-induced heat shock protein protects against renal ischaemia-reperfusion injury in rats - PubMed
Our experiment suggested that a single dose of glutamine could relieve renal ischaemia-reperfusion injury in rats in 24 h, and its mechanism may be associated w

敗血症および肺損傷に対するグルタミンの保護は、熱ショックタンパク質70の発現に依存する。

Glutamine's protection against sepsis and lung injury is dependent on heat shock protein 70 expression - PubMed
Glutamine (GLN) has been shown to protect against inflammatory injury and illness in experimental and clinical settings. The mechanism of this protection is unk

グルタミンの保護作用は用量依存的

Pre-treatment with glutamine attenuates lung injury in rats subjected to intestinal ischaemia-reperfusion - PubMed
Ischaemia-reperfusion injury increases the expression of ICAM-1 in the lung. This may contribute to the migration, accumulation and activation of neutrophils. P
L-スレオニン
L-Threonine induces heat shock protein expression and decreases apoptosis in heat-stressed intestinal epithelial cells - PubMed
This is the first demonstration that THR increases HSP70 and HSP 25 and protects cells from HS. THR's mechanism of protection may involve cytoskeletal stabiliza
亜鉛
Zinc supplementation boosts the stress response in the elderly: Hsp70 status is linked to zinc availability in peripheral lymphocytes - PubMed
Chaperones and zinc are indispensable for proper immune function. All the zinc status, the immune function and the stress response decline during aging. Here we
エストロゲン
Estrogen protects cardiac myogenic (H9c2) rat cells against lethal heat shock-induced cell injury: modulation of estrogen receptor alpha, glucocorticoid receptors, heat shock protein 70, and iNOS - PubMed
In the present study we have established that exposure of rat cardiac myoblasts (H9c2 cells) to 46 degrees C for 1 hour (lethal heat shock) resulted in optimal

薬剤

テプレノン(セルベックス)GGA
ゲラニルゲラニルアセトン/geranylgeranylacetone (GGA)
Geranylgeranylacetone, a noninvasive heat shock protein inducer, induces protein kinase C and leads to neuroprotection against cerebral infarction in rats
Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein (HSP) inducer, against ischemic insult. P…

GGAは、哺乳動物Hsp70-1の発現を誘導する

Geranylgeranylacetone induces heat shock proteins in cultured guinea pig gastric mucosal cells and rat gastric mucosa - PubMed
GGA may induce transcriptional activation of HSP genes, and this novel action may increase gastric mucosal defense at conditions of stress.

GGAの経口投与はAPP23マウスのHSP70レベルを有意に増加させ、アミロイドβ、アミロイドβプラーク沈着、シナプス喪失のレベルの低下させ認知機能の改善を示した。

Suppression of Alzheimer's disease-related phenotypes by geranylgeranylacetone in mice - PubMed
Amyloid-β peptide (Aβ) plays an important role in the pathogenesis of Alzheimer's disease (AD). Aβ is generated by the secretase-mediated proteolysis of β-amylo

経口投与されたGGAのすべての用量(200、400、800 mg / kg /日)は、APPマウスモデルの認知障害を有意に改善しアミロイドβレベルの低下を示した。

また、GGA治療は、低密度リポタンパク質受容体関連タンパク質1(LRP-1)のレベルを増加させ、炎症性サイトカイン(腫瘍壊死因子-α、IL-1β、シクロオキシゲナーゼ-2)レベルを有意に減少させた。

HSP70阻害剤であるケルセチン投与は、ERK/p38 MAPKのリン酸化が促進され大幅に低下した。(24時間の促進と、48~96時間のの抑制の二相性を示す)

Suppression of Alzheimer's disease-related phenotypes by the heat shock protein 70 inducer, geranylgeranylacetone, in APP/PS1 transgenic mice via the ERK/p38 MAPK signaling pathway - PubMed
HSP70 overexpression has a remedying effect in neurodegenerative diseases. In Alzheimer's disease (AD), the suppressive effects of HSP70 overexpression on AD-re

GGAはHSC70のC末端に優先的に結合しHSF-1を解離させる。放出されたHSF-1はリン酸化および活性化され、熱誘導性HSP70遺伝子の熱ショックエレメント(HSE)と結合することが可能となりHSP70発現の誘導をもたらす。

Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology
Geranylgeranylacetone (GGA) is used to treat patients suffering from peptic ulcers and gastritis. We examined the effect of GGA on Helicobacter pylori, which is

GGAはHsp90発現を誘導しeNOSを活性化させた。ラットの脳虚血および再灌流による神経機能異常、脳浮腫、炎症、酸化的損傷、認識機能障害は、用量依存的にGGAにより有意に逆転した。

https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.111.237263
メチレンブルー

メチレンブルー、およびアズールCは、Hsp70のATPアーゼ機能の阻害を介して総タウおよびリン酸化タウのレベルを低下させることができる。

Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo - PubMed
More than 30 neurodegenerative diseases including Alzheimer disease (AD), frontotemporal lobe dementia (FTD), and some forms of Parkinson disease (PD) are chara
Hsp70 ATPase Modulators as Therapeutics for Alzheimer's and other Neurodegenerative Diseases - PubMed
Neurodegenerative diseases caused by abnormal accumulation of the microtubule associated protein tau (MAPT, tau) are collectively called tauopathies. The most d
バルプロ酸

バルプロ酸 Hsp70誘導、抗アポトーシスによる神経保護効果

Valproic acid-mediated Hsp70 induction and anti-apoptotic neuroprotection in SH-SY5Y cells - PubMed
Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, has been reported to exert neuroprotection against a variety of insults. We now show that VPA
アリモクロモル

アリモクロモールは、血液脳関門を効率的に透過し、小胞体常駐型HSP70関連のHSPを誘導することで、リソソーム蓄積症(ゴーシェ病)のグルコセレブロシダーゼのリフォールディング、成熟、およびリソソーム活性を改善する。

The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase
Gaucher Disease is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase fun
ゲルダナマイシン

ゲルダナマイシンはHSP70を誘導、神経原線維変化の形成を抑制することでタウの凝集を抑制した。

Chaperones increase association of tau protein with microtubules - PubMed
Molecular chaperones and their functions in protein folding have been implicated in several neurodegenerative diseases, including Parkinson's disease and Huntin
HSP70の外因的投与
Therapeutic effect of exogenous hsp70 in mouse models of Alzheimer's disease - PubMed
Brain deterioration resulting from "protein folding" diseases, such as the Alzheimer's disease (AD), is one of the leading causes of morbidity and mortality in
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