Therapeutic considerations for APOE and TOMM40 in Alzheimers disease: A tribute to Allen Roses MD
| Autor: | Evans D. Pope, Boris Decourt, Marwan N. Sabbagh, Laura Cordes, Jiong Shi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Amyloid beta Disease Outer mitochondrial membrane Article 03 medical and health sciences 0302 clinical medicine Apolipoproteins E Alzheimer Disease Risk Factors Mitochondrial Precursor Protein Import Complex Proteins medicine Dementia Animals Humans Pharmacology (medical) Alleles Pharmacology Amyloid beta-Peptides biology business.industry Membrane Transport Proteins General Medicine medicine.disease Biochemistry of Alzheimer's disease 030104 developmental biology 030220 oncology & carcinogenesis Expert opinion biology.protein Alzheimer's disease business Neuroscience |
| Zdroj: | Expert Opin Investig Drugs |
| Popis: | Introduction: Four years ago this Autumn, pioneering neurologist Prof. Allen. D. Roses passed away. Hence, we have taken time to reflect on his work and legacy in Alzheimer's disease (AD) research. Prof. Roses rejected the widely accepted amyloid hypothesis, which identifies amyloid beta (Aβ) protein accumulation within the brain as the cause of AD. Instead, he proposed that the epsilon type 4 allele of apolipoprotein (APOE- Ɛ4) and translocase of outer mitochondrial membrane 40 homolog (TOMM40) were preeminent factors in the pathogenesis and progression of AD, particularly in late-onset AD (LOAD). This rejection of the amyloid hypothesis has generated new investigations into APOE and TOMM40 as risk factors for AD. Areas covered: We discuss the contributions of Prof. Roses to AD research, describe how APOE-Ɛ4 and TOMM40 have been posited to trigger neuropathological changes leading to AD, and explore paths to future clinical applications built on the foundations of his research. Expert opinion: The unconventional methodology of targeting APOE and TOMM40 offers great potential for the development of effective preventive and disease-modifying AD interventions. Future preclinical and clinical investigations will greatly benefit from the groundbreaking scientific discoveries of Prof. Roses. |
| Databáze: | OpenAIRE |
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