Synthesis and Biological Evaluation of Novel Ramalin Derivatives as Multi-Target Agents for Alzheimer’s Disease DOI Creative Commons
Tai Kyoung Kim,

Ju‐Mi Hong,

Y. Cho

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(9), P. 2030 - 2030

Published: May 2, 2025

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline, oxidative stress, neuroinflammation, amyloid-beta (Aβ) accumulation, and tau protein hyperphosphorylation. In this study, we synthesized novel Ramalin derivatives evaluated their therapeutic potential against AD, focusing on antioxidant, anti-inflammatory, neuroprotective activities. RA-2OMe, RA-4OMe, RA-2CF3, RA-4OCF3 showed strong antioxidant effects, while RA-2OMe exhibited potent NO NLRP3 inhibition (~20%). RA-NAP, RA-PYD, RA-2Q moderate anti-inflammatory activity. BACE-1 was significant in RA-3CF3, with IC50 values lower than that of positive control, indicating greater inhibitory potency. RA-NAP RA-PYD effectively inhibited both Aβ aggregation, highlighting multi-target for AD therapy. These findings indicate exhibit activity treatment. However, further studies pharmacokinetics, vivo efficacy, long-term safety are required to confirm applicability.

Language: Английский

The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications DOI Open Access
Sehwan Kim, Un Ju Jung, Sang Ryong Kim

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

Citations

5
La maladie de Parkinson : de la génétique aux thérapies ciblées DOI Creative Commons
Guillaume Cogan, Alexis Brice

Comptes Rendus Biologies, Journal Year: 2025, Volume and Issue: 348(G1), P. 21 - 33

Published: Feb. 13, 2025

La maladie de Parkinson (MP) est une multifactorielle impliquant des facteurs génétiques et environnementaux. Cependant, l'âge début, l'étendue lésions la rapidité progression peuvent varier façon considérable, ce qui conduit à s'interroger sur l'unicité MP. L'identification formes monogéniques, dont certaines semblent impliquer mécanismes différents, renforce l'hypothèse distinctes partagent présence d'un syndrome parkinsonien. Alors que le gène SNCA fût premier identifié dans les rares, variants pathogènes gènes GBA1 LRRK2 représentent causes ou risque MP plus communs, PRKN souvent impliqué autosomiques récessives Les patients présentant SNCA, GBA1, diffèrent par leurs caractéristiques cliniques, anatomopathologiques biochimiques. Ainsi, ces quatre associés sont intérêt tout particulier pour développement thérapeutiques spécifiques, d'autant approches actuelles restent symptomatiques. essais cliniques fondés nature du débutent. Dans cette revue, nous présentons principales physiopathologiques avant discuter nouvelles ciblent spécifiquement. Parkinson's disease (PD) is a multifactorial disorder involving various biological pathways. However, it more accurate not to define PD as unique entity, but rather mixture of several diseases with similar phenotypes. Attempts classify subtypes based on the clinical phenotype or biomarkers were tried. Nonetheless, for subset individuals, classification implied gene appears be most practical. Although was first identified in rare patients, pathogenic and are common genetic risk factors PD, frequent autosomal recessive PD. Patients show clinical, anatomopathological biochemical aspects. Therefore, these four genes associated particular interest development targeted therapies. This fact reinforced by reality that current approaches only symptomatic, no curative treatment available today. A number trials aiming slow stop running, involved. In this review, we will discuss therapeutic targeting PRKN.

Citations

0
Peripheral Inflammation and Insulin Resistance: Their Impact on Blood–Brain Barrier Integrity and Glia Activation in Alzheimer’s Disease DOI Open Access
Teresa Ponce-López

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4209 - 4209

Published: April 29, 2025

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and synaptic dysfunction. The accumulation of amyloid beta (Aβ) plaques hyperphosphorylated tau protein leads to neuronal dysfunction, neuroinflammation, glial cell activation. Emerging evidence suggests that peripheral insulin resistance chronic inflammation, often associated with type 2 diabetes (T2D) obesity, promote increased proinflammatory cytokines, oxidative stress, immune infiltration. These conditions further damage the blood-brain barrier (BBB) integrity neurotoxicity This induces neuroinflammation impaired signaling, reducing glucose metabolism exacerbating Aβ hyperphosphorylation. Indeed, epidemiological studies have linked T2D obesity an risk developing AD, reinforcing connection between metabolic disorders neurodegeneration. review explores relationships resistance, BBB highlighting their role in activation exacerbation AD pathology.

Language: Английский

Citations

0
Synthesis and Biological Evaluation of Novel Ramalin Derivatives as Multi-Target Agents for Alzheimer’s Disease DOI Creative Commons
Tai Kyoung Kim,

Ju‐Mi Hong,

Y. Cho

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(9), P. 2030 - 2030

Published: May 2, 2025

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline, oxidative stress, neuroinflammation, amyloid-beta (Aβ) accumulation, and tau protein hyperphosphorylation. In this study, we synthesized novel Ramalin derivatives evaluated their therapeutic potential against AD, focusing on antioxidant, anti-inflammatory, neuroprotective activities. RA-2OMe, RA-4OMe, RA-2CF3, RA-4OCF3 showed strong antioxidant effects, while RA-2OMe exhibited potent NO NLRP3 inhibition (~20%). RA-NAP, RA-PYD, RA-2Q moderate anti-inflammatory activity. BACE-1 was significant in RA-3CF3, with IC50 values lower than that of positive control, indicating greater inhibitory potency. RA-NAP RA-PYD effectively inhibited both Aβ aggregation, highlighting multi-target for AD therapy. These findings indicate exhibit activity treatment. However, further studies pharmacokinetics, vivo efficacy, long-term safety are required to confirm applicability.

Language: Английский

Citations

0