Neurodegeneration in leprosy: Insights from model systems and patients

Abstract

Despite the long history of leprosy as an infectious disease it remains a public health problem and millions are living with disability due to past or present leprosy. Disabilities due to nerve function loss, the pathologic hallmark of this infection, are associated directly with injury to the peripheral nervous system (PNS), which is primarily caused by the unique capacity of leprosy bacteria to invade Schwann cells, the glial cells of the PNS. Recent studies have suggested that Mycobacterium leprae i nterfere with Schwann cell signaling system and functions, which subsequently facilitates bacterial propagation due to concomitant Schwann cell de-differentiation. While these alterations during the long bacterial incubation period abrogate normal glial and neuronal functions, they also engender acute inflammatory responses that eventually destroy the peripheral nerves. Although the latter manifests clinically as sensorimotor loss and enable the diagnosis of patients with nerve damage, the underlying early events of nerve infection and inflammatory responses that cause the nerve injury are not well understood. These are the major challenges if we are to develop effective early diagnostics and new therapeutics for this devastating neglected disease. Here we highlight the recent knowledge on the early infectious process obtained in model systems and present those findings in the context of available clinical fi ndings from leprosy patients.