ABSTRACT
Hypothesis: DHA-laden membranes play cardinal roles in modulating the health and causing the death of neurons.
Dramatic advances have been made in understanding the molecular pathology of agerelated neurodegenerative diseases such as Alzheimer’s disease (AD; Figure 20.1). Four of the most widely accepted unifying factors linking brain diseases in general are (1) oxidative stress, (2) energy stress, (3) toxic peptides, and (4) apoptosis. We present evidence in this chapter suggesting DHA membranes serve as a fth unifying factor of age-related neurodegenerative diseases. Indeed, classifying these diseases as membrane diseases subject to the DHA principle provides a framework for possible integration of all ve of these factors. According to this membrane hypothesis oxidative stress, energy stress, and toxic peptides all work together to modulate what we term membrane structural homeostasis. Membrane structural homeostasis is envisioned as comprising multiple parameters, including DHA levels, saturated fatty acid levels, cholesterol levels, and so forth, all aimed at maintaining a healthy long-term environment to facilitate membrane biochemistry. A critical corollary of the DHA principle is that large deviations in the physical state of the bilayers of neurons, such as caused by depletion of DHA, will gradually lead to catastrophic consequences (i.e., neuron death), a time clock that can be accelerated or slowed down by both internal and external signals (e.g., Parkinsonian chemicals and toxic prion peptides). Recent data even implicate DHA-enriched membranes in the nal stages of suicide or destruction of sensory axons.
