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Figure 6 | Molecular Neurodegeneration

Figure 6

From: A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1

Figure 6

a working model for dynein mutant protection against SOD1-ALS. We propose that dynein mutations provide neuroprotection by converging paths. First, degeneration of proprioceptive neurons (PN) modify network activity (1) by decreasing direct glutamatergic input to motor neurons (MN), but also to inhibitory interneurons (IN). Second, CNS-linked hyperactivity (2) might on its own lead to increased motoneuronal activity, and MMP9 activation. Last, by modifying energy metabolism and favoring carbohydrate oxidation over lipid oxidation (3), dynein mutation reverts the energy deficit of SOD1(G93A) mice, thereby increasing IGF-1 production in the liver. This increased IGF-1 production is able to enter the CNS due to MMP9 activation. Other circulating factors might also increase IGF-1 supply to motor neurons.

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Molecular Neurodegeneration

ISSN: 1750-1326