aβ(1-42)

Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

Gamma-secretase modulator 2 is a potent, selective compound for the treatment of Alzheimer's disease, specifically designed to modulate γ-secretase activity. This modulation selectively attenuates the production of Aβ(1-42), addressing diseases associated with Aβ deposition in the brain, particularly Alzheimer's disease.

Amyloid-β-IN-1 (compound 13), a synthetic peptide featuring the hydrophobic C-terminal segment VVIA-NH2 and its reversed sequence AIVV-NH2 derived from Aβ 42, acts as an Aβ inhibitor. It effectively inhibits Aβ aggregation and exhibits neuroprotective effects.

SEN-1269 is an amyloid-β (AB) aggregation inhibitor that acts by blocking Aβ(1-42) aggregation and protecting neuronal cell lines exposed to Aβ(1-42), reducing Aβ oligomer-induced LTP and memory deficits in vivo.

Tabersonine (Tabersonin)is a terpene indole alkaloid found in the medicinal plant Catharanthus roseus.

Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-amino acid protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease.1,2,3Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers.1Aβ42 accumulates in the brain of many transgenic mouse models of Alzheimer's disease and, in many models, the onset of amyloid deposition positively correlates with deficits in spatial learning and memory.4 1.Wolfe, M.S.Therapeutic strategies for Alzheimer's diseaseNat. Rev. Drug Discov.1(11)859-866(2002) 2.Iwatsubo, T., Odaka, A., Suzuki, N., et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron13(1)45-53(1994) 3.Hardy, J.A., and Higgins, G.A.Alzheimer's disease: The amyloid cascade hypothesisScience256(5054)184-185(1992) 4.Jankowsky, J.L., and Zheng, H.Practical considerations for choosing a mouse model of Alzheimer's diseaseMol. Neurodegener.12(1)89(2017)

Amyloid-β (25-35) (Aβ (25-35)) is an 11-residue fragment of the Aβ protein that retains the physical and biological characteristics of the full length peptide. It forms fibrils that react to thioflavin T and Congo red and are organized in a cross-β arrangement of β-strands similar to Aβ (1-40) and Aβ (1-42) fibrils. Aggregated Aβ (25-35) decreases the viability of rat adrenal PC12 cells. It also decreases the viability of primary rat cortical neurons at concentrations ranging from 1 nM to 30 μM. In vivo, intracerebral injection of Aβ (25-35) (20 nmol) in rats induces lesions of neuronal and tissue loss. Aggregated Aβ (25-35) administered intracerebroventricularly to rats induces learning and memory impairments in the Y-maze, novel object recognition, and contextual fear conditioning tests.

Aβ tau aggregation-IN-1 is a potent inhibitor of Aβ 1-42 β-sheet formation and tau aggregation, exhibiting K D values of 160 μM and 337 μM with Aβ 1-42 and tau, respectively. Additionally, Aβ tau aggregation-IN-1 efficiently penetrates the blood-brain barrier.

1. N-trans-Feruloyltyramine (Feruloyltyramine)(NTF) has hepatoprotective effect. 2. NTF has antioxidative activity against Aβ(1-42)-induced neuronal death. 3. NTF is likely to inhibit COX enzymes, thereby suppressing P-selectin expression on platelets, is a platelet aggregation inhibitor. 4. NTF inhibits melanogenesis in a dose-dependent manner, NTF induces downregulation of tyrosinase resulted in suppression of melanin biosynthesis in murine B16 melanoma cells.

β-Secretase Inhibitor II is a tripeptide aldehyde inhibitor of β-Secretase with an inhibitory potency of IC50 = 700 nM against total Aβ and IC50 = 2.5 μM against Aβ[1-42]. This compound, with a simple structure, is particularly useful in Alzheimer's disease research.

TABERSONINE HYDROCHLORIDE is a natural product extracted from the bean of Voacanga africana, is a potent inhibitor against Aβ(1 42) aggregation and toxicity.

ChE Aβ1-42-IN-1 (compound 28) is a potent aggregation inhibitor of ChE and Aβ1-42 with excellent BBB permeability, exhibiting IC50 values of 0.062 μM for AChE, 0.767 μM for BuChE, and 1.227 μM for Aβ1-42 aggregation. ChE Aβ1-42-IN-1 is a potent multi-targeted anti-Alzheimer's disease agent [1].

HDAC6-IN-6 (compound 6a) is a potent HDAC6 inhibitor with an IC50 value of 0.025 μM that can penetrate the BBB. It exhibits strong inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM, respectively. HDAC6-IN-6 also enhances neurite outgrowth without significant neurotoxicity [1].

BuChE-IN-6 (compound 1b) is a highly effective and specific inhibitor of BuChE (butyrylcholinesterase), with IC50 values of 0.46 μM for eqBuChE and 0.51 μM for hBuChE. Additionally, it inhibits the self-aggregation of Aβ 42 [1].

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50 = 0.025 μM) that inhibits Aβ 1-42 self-aggregation and AChE with IC50 values of 3.0 and 0.72 μM, respectively. Additionally, HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

NXPZ-2 is an orally active Keap1-Nrf2 protein-protein interaction (PPI) inhibitor (Ki: 95 nM, EC50: 120 and 170 nM). NXPZ-2 dose-dependently attenuates Aβ[1-42]-induced cognitive disturbances, enhances neuronal number and function, and improves pathological alterations in the brain of Alzheimer's disease (AD) mice. NXPZ-2 has potential for studies of Keap1-Nrf2 PPI inhibitors and AD-related disorders.

Antioxidant agent-8, an orally active compound, inhibits Aβ 1-42 deposition by preventing fibril aggregation (IC 50 = 11.15 µM) and aiding in fibril disaggregation (IC 50 = 6.87 µM). It counteracts Cu2+-induced Aβ 1-42 fibril aggregation and disaggregation with lower IC 50 values of 3.69 µM and 3.35 µM, respectively. Additionally, it exhibits antioxidant and anti-inflammatory activities, demonstrates biosafety and blood-brain barrier permeability, and provides a neuroprotective effect.

AChE BuChE-IN-1, a selective butyrylcholinesterase (BuChE) inhibitor derived from chrysin, exhibits a potent efficacy with an IC50 of 0.48 μM against BuChE and a lesser inhibitory effect on acetylcholinesterase (AChE) with an IC50 of 7.16 μM. It demonstrates significant hydroxyl radical (·OH) scavenging activity, achieving an IC50 of 0.1674 μM, and effectively inhibits reactive oxygen species (ROS) and Aβ 1-42 aggregation, including self-aggregation, copper (Cu 2+)-induced, and AChE-induced aggregation. Characterized by high blood-brain barrier (BBB) permeability, bioavailability, and low cellular toxicity, AChE BuChE-IN-1 holds promising potential for Alzheimer's disease (AD) research.

MAO-B-IN-21 is an MAO-B inhibitor characterized by superior antioxidant and anti-Aβ aggregation activities, metal-ion chelating capabilities, and mitigation of neuroinflammation (NO, TNF-α). It demonstrates neuroprotective effects with notable BBB permeability and, in an Aβ1-42 induced Alzheimer's disease mouse model, significantly enhances memory and cognitive functions [1].

LPYFD-NH2 TFA, a pentapeptide, inhibits Aβ(1-42) aggregation, indicating its potential utility in Alzheimer's disease research [1].

Chemerin-9 (149-157) TFA is a potent CMKLR1 (chemokine-like receptor 1) agonist with anti-inflammatory properties. It activates phosphorylation of Akt and ERK and induces ROS production, beneficially modulating immune responses, adipocyte differentiation, and glucose metabolism. Additionally, it has been shown to alleviate Aβ 1-42-induced memory impairment, highlighting its therapeutic potential [1] [2] [3] [4].

Amyloid 17-42 (Aβ(17-42)), a significant component of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid in Down's syndrome, results from alpha- and gamma-secretase cleavage of amyloid precursor protein (APP) and can trigger neuronal apoptosis via the Fas-like caspase-8 activation pathway [1].

(Gly22)-Amyloid β-Protein (1-42), a peptide fragment of Amyloid β-Protein (Aβ), plays a crucial role in Alzheimer's disease by forming the main component of vascular and parenchymal amyloid deposits. The Glu22 to Gly22 mutation in Aβ is known to enhance aggregation [1] [2].

(Glu20)-Amyloid β-Protein (1-42) represents a variant of amyloid β-protein (Aβ) that fibrillizes more slowly due to the Glu20 mutation, which diminishes Aβ42's tendency to aggregate and inhibits the accumulation of this slowly fibrillizing peptide. Amyloid β-protein is the principal constituent of amyloid deposits in the vascular system and brain parenchyma in Alzheimer's disease [1] [2].