Chronic intranasal deferoxamine ameliorates motor defects and pathology in the α-synuclein rAAV Parkinson's model

Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson’s disease

“…Furthermore, we observed that pathological ASYN + aggregations in terminals developed with time, in number and size. In agreement with our previous work 36 , we noted that there were fewer VMAT2 + pathological accumulations than TH + or human ASYN + accumulations, suggesting that abnormal assembly of VMAT2 is secondary to that initiated by ASYN, followed by TH deposition and lastly, but not always, by VMAT2 to finally result in axonal loss. As previously reported in the model, we did not observe any accumulation of DAT in these swellings, maybe due to localization of DAT in the cytoplasmic membrane vs. the intracytoplasmic location of TH and VMAT2 9 .…”

“…Morphologically similar axonal pathology has been revealed by ASYN immunostaining in postmortem PD studies 48–50 . These axonal striatal swellings contained proteinase-K resistant ASYN + , an accepted marker of fibrillar insoluble ASYN, commonly used in human postmortem pathology 51–53 and in animal models 8, 36, 53, 54 . Interestingly, proteinase-K resistant ASYN seems to selectively locate first in presynaptic terminals highlighting its possible role in synaptic dysfunction 55 .…”

Deferoxamine-mediated up-regulation of HIF-1α prevents dopaminergic neuronal death via the activation of MAPK family proteins in MPTP-treated mice

“…This concept receives support from various animal PD models, wherein a number of iron chelators have been shown to be protective against dopaminergic neuron loss (Ben- Shachar, et al, 1991, Febbraro, et al, 2013, Kaur, et al, 2003, Lv, et al, 2014, You, et al, 2015, Zhang, et al, 2012. To date, the most widely used chelator in clinical settings for the treatment of iron overload is desferrioxamine (DFO).…”

Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation

“…Intranasal (IN) delivery is a non-invasive method of targeting drugs directly from the nose to the brain, and allows for DFO to be delivered with minimal systemic exposure. Intranasal delivery of DFO has been shown to have benefit in several animal models of Alzheimer's and Parkinson's disease [7][8][9][10]. Hanson et al [8] showed a behavioral benefit of IN DFO in an amyloid mouse model, though it did not address any biochemical mechanisms, and behavioral analysis was limited to a single memory task.…”