Mutations in α-synuclein cause some cases of familial PD. Several lines of transgenic mice that overexpress wild type or mutant human α-synuclein exhibit progressive accumulation of α-synuclein in neurons, motor dysfunction and death (Crabtree and Zhang, 2012). Mice expressing mutant (A53T) α-synuclein exhibit impaired autonomic regulation of heart rate characterized by elevated resting heart rate associated with accumulation of α-synuclein aggregates in the brainstem and reduced parasympa-thetic (cardiovagal) tone (Griffioen et al., 2013). Maintenance of the α-synuclein mutant mice on ADF reversed the autonomic deficit, whereas a high fat diet exacerbated the autonomic deficit (Griffioen et al., 2013). Consistent with the latter findings, a high fat diet hastened the onset of motor dysfunction and brainstem pathology in another line of α-synuclein mutant mice, which was associated with reduced activity of kinases known to be involved in neurotrophic factor signaling (Rotermund et al., 2014). In addition to enhancement of neurotrophic factor/BDNF signaling, IF may counteract PD-related pathogenic processes by stimulating autophagy. Indeed, inhibition of mTOR with rapamycin, which stimulates autophagy, reduced oxidative stress and synaptic damage, and improved motor function in a α-synuclein accumulation-based mouse model of PD (Bai et al., 2015).

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