Iron Overload, Microbleeding and the Role of Bilirubin in Alzheimer’s Disease Brain: Revisiting the Vascular Hypothesis DOI Open Access
Eleonora Ficiarà,

Rosita Rabbito,

Fausto Roveta

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3060 - 3060

Published: March 27, 2025

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most prevalent forms of dementia, sharing overlapping clinical features yet distinct pathophysiological mechanisms. While AD is primarily driven by amyloid-beta (Aβ) plaques tau neurofibrillary tangles, VaD results from cerebrovascular pathology, including ischemic lesions chronic hypoperfusion. However, accumulating evidence suggests that dysfunction a crucial contributor to both conditions, bridging neurodegenerative pathologies. In this review, we explore interplay between VaD, focusing on shared pathways such as blood-brain barrier (BBB) breakdown, neuroinflammation, microvascular damage. Notably, cerebral microbleeds have emerged common feature in further linking pathology neurodegeneration. Microbleeding contributes BBB disruption, iron deposition, exacerbated oxidative stress, creating vicious cycle accelerates cognitive decline. We highlight role dysregulation key driver AD, exacerbating Aβ accumulation, hyperphosphorylation, ferroptosis. Conversely, bilirubin emerges molecule with theranostic potential, acting biomarker neuroprotective agent due its antioxidant anti-inflammatory properties. Despite protective role, bilirubin's under pathological conditions may contribute damage neurovascular dysfunction. context, accumulation recurrent disrupt homeostasis, amplifying injury inflammation. propose hypothesis integrates metabolism suggesting their imbalance plays central pathogenesis worsening. Understanding intricate molecular neurodegeneration could provide novel insights into targeted interventions aimed at mitigating Finally, discuss potential bilirubin-based therapeutic strategies, counteracting stress modulating neuroinflammatory pathways, offering promising avenues for future research precision medicine dementia.

Language: Английский

Unveiling the role of Na⁺/K⁺-ATPase pump: neurodegenerative mechanisms and therapeutic horizons DOI

Ramandeep Kaur Sidhu,

Kousik Maparu,

Shamsher Singh

et al.

Pharmacological Reports, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Language: Английский

Citations

0
Iron Overload, Microbleeding and the Role of Bilirubin in Alzheimer’s Disease Brain: Revisiting the Vascular Hypothesis DOI Open Access
Eleonora Ficiarà,

Rosita Rabbito,

Fausto Roveta

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3060 - 3060

Published: March 27, 2025

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most prevalent forms of dementia, sharing overlapping clinical features yet distinct pathophysiological mechanisms. While AD is primarily driven by amyloid-beta (Aβ) plaques tau neurofibrillary tangles, VaD results from cerebrovascular pathology, including ischemic lesions chronic hypoperfusion. However, accumulating evidence suggests that dysfunction a crucial contributor to both conditions, bridging neurodegenerative pathologies. In this review, we explore interplay between VaD, focusing on shared pathways such as blood-brain barrier (BBB) breakdown, neuroinflammation, microvascular damage. Notably, cerebral microbleeds have emerged common feature in further linking pathology neurodegeneration. Microbleeding contributes BBB disruption, iron deposition, exacerbated oxidative stress, creating vicious cycle accelerates cognitive decline. We highlight role dysregulation key driver AD, exacerbating Aβ accumulation, hyperphosphorylation, ferroptosis. Conversely, bilirubin emerges molecule with theranostic potential, acting biomarker neuroprotective agent due its antioxidant anti-inflammatory properties. Despite protective role, bilirubin's under pathological conditions may contribute damage neurovascular dysfunction. context, accumulation recurrent disrupt homeostasis, amplifying injury inflammation. propose hypothesis integrates metabolism suggesting their imbalance plays central pathogenesis worsening. Understanding intricate molecular neurodegeneration could provide novel insights into targeted interventions aimed at mitigating Finally, discuss potential bilirubin-based therapeutic strategies, counteracting stress modulating neuroinflammatory pathways, offering promising avenues for future research precision medicine dementia.

Language: Английский

Citations

0