Abstract
Although amyotrophic lateral sclerosis (ALS) has been considered as a disorder of the motor neuron (MN) cell body, recent evidences show the non-cell-autonomous pathogenic nature of the disease. Axonal degeneration, loss of peripheral axons and destruction of nerve terminals are early events in the disease pathogenic cascade, anticipating MN degeneration, and the onset of clinical symptoms. Therefore, although ALS and peripheral axonal neuropathies should be differentiated in clinical practice, they also share damage to common molecular pathways, including axonal transport, RNA metabolism and proteostasis. Thus, an extensive evaluation of the molecular events occurring in the peripheral nervous system (PNS) could be fundamental to understand the pathogenic mechanisms of ALS, favoring the discovery of potential disease biomarkers, and new therapeutic targets.
Highlights
Amyotrophic lateral sclerosis (ALS) is the most common and severe form of motor neuron disease (MND), an heterogeneous group of disorders defined by prominent motor neuron (MN) degeneration (Saberi et al, 2015; Riva et al, 2016)
In clinical practice MNDs should be differentiated from other peripheral nervous system (PNS) disorders, sensory and autonomic neurons in the dorsal root ganglia (DRG) and lower MNs in the ventral horns share important challenges, as proper stability and functioning of their long projections throughout the body requires a protective environment and efficient communication between the central nervous system (CNS) and the outermost areas of these cells
In patients presenting with isolated signs of lower MN (LMN) involvement (LMN Syndrome – LMNS), the differential diagnosis may be more challenging since the primary disease target may be the cell soma, the axon and its myelin, the neuromuscular junction (NMJ) or the muscle (Riva et al, 2011b; Garg et al, 2017; Muller et al, 2018)
Summary
Amyotrophic lateral sclerosis (ALS) is the most common and severe form of motor neuron disease (MND), an heterogeneous group of disorders defined by prominent motor neuron (MN) degeneration (Saberi et al, 2015; Riva et al, 2016). In patients presenting with isolated signs of LMN involvement (LMN Syndrome – LMNS), the differential diagnosis may be more challenging since the primary disease target may be the cell soma, the axon and its myelin, the neuromuscular junction (NMJ) or the muscle (Riva et al, 2011b; Garg et al, 2017; Muller et al, 2018). Such disorders share the motor unit as a common target of damage, but may be potentially underpinned by common pathogenic mechanisms. Capacity and may present signs of myelin damage, inflammation, or pathologic deposits (Benedetti et al, 2010)
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