Energy metabolism in ALS: an underappreciated opportunity?

Abstract

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal neurodegenerative disorder that primarily affects motor neurons. Despite our increased understanding of the genetic factors contributing to ALS, no effective treatment is available. A growing body of evidence shows disturbances in energy metabolism in ALS. Moreover, the remarkable vulnerability of motor neurons to ATP depletion has become increasingly clear. Here, we review metabolic alterations present in ALS patients and models, discuss the selective vulnerability of motor neurons to energetic stress, and provide an overview of tested and emerging metabolic approaches to treat ALS. We believe that a further understanding of the metabolic biology of ALS can lead to the identification of novel therapeutic targets.

Nuclear lipidome is altered in amyotrophic lateral sclerosis: a preliminary study

“…Up to date, no previous evidence of its involvement in this disease were known, except with the fact that PKC levels were increased in ALS patients [29]. The involvement of the potential loss of PKCßII in ALS pathogenesis can be diverse, as this protein interacts with mitochondria [30], and with autophagic function [31], to name a few, and both elements are involved in ALS [32,33] Other changes in lipid components of nuclei include plasmalogens. These membrane glycerophospholipids contain a fatty alcohol with a vinyl-ether bond at the sn-1 position, and they are enriched in polyunsaturated fatty acids at the sn-2 position of the glycerol backbone.…”

ALSUntangled 53: Carnitine supplements

“…Mitochondria produce energy for cells by metabolizing various compounds obtained from food. Alterations in neuronal mitochondrial function, resulting in impaired intracellular energy production, are hypothesized to be important in ALS pathophysiology (34,35). In a clinical trial of healthy participants, intravenous supplementation with ALCAR, PLC, and to a lesser extent LC increased blood levels of the energy equivalent ATP (36).…”

“…It should be noted though that even if carnitine supplementation can improve mitochondrial energy production, this does not mean it will have clinical benefits for PALS. Prior efforts to improve mitochondrial function with other theoretically promising pharmaceuticals failed to show benefits (34,35).…”

“…In spite of this possibly causal association, clinical trials have suggested that LC supplementation lowers the risk of all-cause mortality following a myocardial infarction (86) and has some benefit in heart failure (67) and type 2 diabetes mellitus (87,88). Abnormalities of energy metabolism in PALS (35) likely changes this risk, but the relationship is unknown.…”

Saccharide‐based nanocarriers for targeted therapeutic and diagnostic applications

“…monosaccharides, disaccharides, oligosaccharides and polysaccharides), and they perform versatile roles in living organisms . For example, polysaccharides serve as energy storage or as structural components, while the 5‐carbon monosaccharide ribose is an essential component of coenzymes . Basically, saccharides and their derivatives play vital roles in the immune and reproductive systems, and they are also essential in sustaining life for they serve as the main source of energy in the human body.…”