Oxidative stress and neurodegeneration

JM PASQUINI; PASQUINI LA; HR QUINTÁ

Biochemistry in health and disease

Springer, New York

Año: 2016; p. 1 - 443

Central nervous system (CNS) demyelinating diseases exhibit a wide range of clinical presentations, with different pathological findings, temporal evolution, severity and response to treatment. Among them, multiple sclerosis (MS), a highly disseminated, chronic, inflammatory demyelinating disease, entails progressive neuroaxonal degeneration and is one of the most common causes of progressive disability affecting young people. Despite variable disease courses, most patients initially present a relapsing-remitting pattern (relapsing-remitting MS; RRMS). After 10-15 years, this pattern becomes progressive in up to 50% of untreated patients, with clinical symptoms slowly but constantly causing deterioration over a period of many years (secondary progressive MS; SPMS). In about 15% MS patients, however, disease progression is relentless as from onset (primary progressive MS; PPMS). The transition to a progressive disease course is thought to occur when a threshold of neuronal and axonal loss is reached and the compensatory capacity of the CNS is surpassed. Abundant evidence supports the notion that axonal degeneration and neuronal loss, rather than the inflammation per se, are the main pathophysiological substrates of permanent clinical deficits [1, 2]. Although the clinical sequelae of axonal loss are more apparent in the later stages of MS, axonal injury occurs early in acute MS lesions [3]. Despite the fact that demyelination with loss of trophic support from oligodendrocytes clearly contributes to axonal degeneration [4, 5], both axonal and neuronal injury may occur without demyelination [6-11].