The Carnitine Palmitoyl-Transferase 2 Cascade Hypothesis for Alzheimer’s Disease

Author:

Keizer Hiskias G.12ORCID,Brands Ruud123,Oosting Ronald S.12,Seinen Willem123

Affiliation:

1. Alloksys Biotechnology, Wageningen, The Netherlands

2. AMRIF Biotechnology, Wageningen, The Netherlands

3. Institute for Risk Assessment Sciences (IRAS), Utrecht, The Netherlands

Abstract

Despite decades of intense research, the precise etiology of Alzheimer’s disease (AD) remains unclear. In this hypothesis, we present a new perspective on this matter by identifying carnitine palmitoyl transferase-2 (CPT2) as a central target in AD. CPT2 is an enzyme situated within the inner mitochondrial membrane, playing a crucial role in beta-oxidation of fatty acids. It exhibits high sensitivity to hydrogen peroxide. This sensitivity holds relevance for the etiology of AD, as all major risk factors for the disease share a commonality in producing an excess of hydrogen peroxide right at this very mitochondrial membrane. We will explain the high sensitivity of CPT2 to hydrogen peroxide and elucidate how the resulting inhibition of CPT2 can lead to the characteristic phenotype of AD, thus clarifying its central role in the disease’s etiology. This insight holds promise for the development of therapies for AD which can be implemented immediately.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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