Browsing by Author "Korpikoski, Jaan"

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motoneurons (MN) within the central nervous system (CNS), leading to muscle atrophy and eventual paralysis. Cause of death is in most cases due to respiratory failures 3-5 years after diagnosis. ALS can occur idiopathically without any know causes or it can be associated with certain genetic mutations. One of these known factors is a point mutation in the superoxide dismutase 1 (SOD1) gene, particularly the G93A mutation is known to affect the functionality of SOD1. SOD1 is an enzyme that metabolizes reactive oxygen species (ROS) and the SOD1-G93A mutation limits this functionality and propagates endoplasmic reticulum (ER) stress signalling cascades. Mutated SOD1 cannot be broken down by the cell, and hence it is associated with activation of protein degradation (ERAD) system with a prolonged ER stress signalling, followed by apoptotic cellular response. Although SOD1-G93A mutation has been widely studied, the basic mechanisms of the disease are not fully understood. Mesencephalic astrocyte derived neurotrophic factor (MANF) is an evolutionary conserved protein with trophic properties. MANF has been researched as novel treatment in a range of neurodegenerative diseases, such a Parkinson’s. MANF has been shown to promote cell survival but has limitation as an administered drug treatment. In this study we used transgenic SOD1-G93A mouse model with male mice to study the effects of a novel MANF variant for ALS. Disease progression and histology were used to assess the treatment efficacy.