The Neuroprotective and Neurodegeneration Effects of Heme Oxygenase-1 in Alzheimer's Disease.
J Alzheimers Dis
; 78(4): 1259-1272, 2020.
Article
en En
| MEDLINE
| ID: mdl-33016915
Alzheimer's disease (AD) is a neurodegenerative disease characterized by complex pathological and biological features. Notably, extracellular amyloid-ß deposits as senile plaques and intracellular aggregation of hyperphosphorylated tau as neurofibrillary tangles remain the primary premortem criterion for the diagnosis of AD. Currently, there exist no disease-modifying therapies for AD, and many clinical trials have failed to show its benefits for patients. Heme oxygenase 1 (HO-1) is a 32âkDa enzyme, which catalyzes the degradation of cellular heme to free ferrous iron, biliverdin, and carbon monoxide under stressful conditions. Several studies highlight the crucial pathological roles of HO-1 in the molecular processes of AD. The beneficial roles of HO-1 overexpression in AD brains are widely accepted due to its ability to convert pro-oxidant heme to biliverdin and bilirubin (antioxidants), which promote restoration of a suitable tissue redox microenvironment. However, the intracellular oxidative stress might be amplified by metabolites of HO-1 and exacerbate the progression of AD under certain circumstances. Several lines of evidence have demonstrated that upregulated HO-1 is linked to tauopathies, neuronal damage, and synapse aberrations in AD. Here, we review the aspects of the molecular mechanisms by which HO-1 regulates AD and the latest information on the pathobiology of AD. We further highlight the neuroprotective and neurodystrophic actions of HO-1 and the feasibility of HO-1 as a therapeutic target for AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Hemo-Oxigenasa 1
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos