Amyotrophic lateral sclerosis is not only a motor neuron disease: impact of the sympathoadrenal axis

Amyotrophic lateral sclerosis (ALS), an adult onset, fatal neurodegenerative disease, has as a cardinal pathogenic feature the selective death of motor neurons (MNs) at cortex, brainstem, and spinal cord. In this review we focus on four aspects: (i) hypothesis disease propagation through cerebrospinal fluid (CSF); (ii) distortion exocytotic release neurotransmitters sympathoadrenal axis; (iii) ultrastructural functional alterations mitochondria from adrenal medullary chromaffin cells (CCs); (iv) purinergic P2X7 receptor (P2X7R) potential target for neuroprotection. Concerning one to another area central nervous system (CNS), pattern clinical progression suggests that spreads centrifugally. This indicates kind toxin agent may be released propagated CSF. our laboratory found CSF ALS patients exerted toxic effects cultured cortical MNs. CCs, deep distortions kinetics fusion pore in process catecholamine release, SOD1G93A mouse model ALS. Furthermore, these could related accumulation mutated SOD1 into mitochondria; resulted mitochondrial depolarization, excess production reactive oxygen species deficiency oxidative phosphorylation. Finally, discuss recent data therapeutic effect compound JNJ-47965567, blocker P2X7Rs known central-stage neuroinflammation. Upon its chronic administration SOD1G93A, delayed onset but only females mice. conclusion, why MN selectively die remains mystery; On other hand, it seems cell types are also affected, particularly axis. As pathogenesis obscure, search targets slow ALS, puzzling.