This manuscript reviews the role of membrane trafficking and retromer complex in Parkinson’s and Alzheimer’s. I find the topic interesting to the scientific audience of the journal and well written. The literature review is sound, and ideas flow logically from one section to the next. However, some areas need improvement to strengthen the article before publication. Therefore the authors could:
1. provide more information on pharmacological chaperons and cite corresponding original studies.
2. explain why increasing retromer levels could be a practical and safe approach. They have to provide more details about studies that have shown the restoration of neurotoxic consequences in models of AD and PD without harmful side effects.
3. elaborate on the findings that VPS35 deficiency leads to neuron loss and dopamine neuron loss in animal models.
4. discuss additional studies demonstrating the neuroprotective effects of elevating VPS35 levels, such as the lentivirus-mediated human VPS35 overexpression in transgenic mice that reverses synuclein-induced neurotoxicity.