What is "Hyper" in the ALS Hypermetabolism?

Alberto Ferri,Roberto Coccurello

doi:10.1155/2017/7821672

Abstract

The progressive and fatal loss of upper (brain) and lower (spinal cord) motor neurons and muscle denervation concisely condenses the clinical picture of amyotrophic lateral sclerosis (ALS). Despite the multiple mechanisms believed to underlie the selective loss of motor neurons, ALS aetiology remains elusive and obscure. Likewise, there is also a cluster of alterations in ALS patients in which muscle wasting, body weight loss, eating dysfunction, and abnormal energy dissipation coexist. Defective energy metabolism characterizes the ALS progression, and such paradox of energy balance stands as a challenge for the understanding of ALS pathogenesis. The hypermetabolism in ALS will be examined from tissue-specific energy imbalance (e.g., skeletal muscle) to major energetic pathways (e.g., AMP-activated protein kinase) and whole-body energy alterations including glucose and lipid metabolism, nutrition, and potential involvement of interorgan communication. From the point of view here expressed, the hypermetabolism in ALS should be evaluated as a magnifying glass through which looking at the ALS pathogenesis is from a different perspective in which defective metabolism can disclose novel mechanistic interpretations and lines of intervention.

Highlights

We may just portray amyotrophic lateral sclerosis (ALS) as a progressive and rapid degeneration of upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex
From the point of view here expressed, the hypermetabolism in ALS should be evaluated as a magnifying glass through which looking at the ALS pathogenesis is from a different perspective in which defective metabolism can disclose novel mechanistic interpretations and lines of intervention
In the light of extensive experimental evidence, it is possible to conclude that mitochondrial dysfunction in ALS is not restricted to motor neurons and it appears clearly that the oxidative alterations observed in skeletal muscles are relevant to the progression of the disease

Summary

Introduction

We may just portray amyotrophic lateral sclerosis (ALS) as a progressive and rapid degeneration of upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex This precise, though laconic, clinical picture instantly seizes our attention on the gradual loss of motor function that ends with skeletal muscle atrophy, paralysis, and death. Different mutated genes have been discovered in familial cases of ALS and, in addition to the well-known mutations of Sod gene, multiple animal models were generated to mimic the disease. In this view, since fALS and sALS are clinically overlapping, the genetic models might help to shed light on the more frequent sporadic form of the disease

Muscle Atrophy and Energy Consumption

Defective Energy Metabolism in ALS

The Bioenergetic Engine

Findings

Energy Sensor and Fuel Switch