Iron Homeostasis in the CNS: An Overview of the Pathological Consequences of Iron Metabolism Disruption

Round 1

Reviewer 1 Report

It is a well written review and should be of interest to broader audience involved in studying the role of iron in diseases. Iron has been shown to play an important role in bacterial pathogenesis and host mediated immunity by releasing various iron chelating siderophores in the region of bacterial infection thereby aiding in  host defense.  The bacteria also responds by releasing similar iron chelators and this co-evolution between the bacteria and host is very fascinating to study.

In this review, the authors have compared both the scenarios: the  consequence of iron deficiency as well as iron accumulation in neurodegenerative diseases. Iron acts as important co-factor for enzymes involved in  central carbon metabolism by binding as a Fe-S clusters. The clusters are sensitive to oxidative damage by superoxides (ROS) that are typically produced under pathological conditions and causes the  conversion of active holo form of the protein to inactive apo-form. Moreover, superoxides are also produced by Fenton reaction inside the cell causes significant changes in the proteome. On, the otherhand, the accumulation of iron has been shown be associated with various neurodegenerative diseases. In this review, the authors have very nicely explained the consequences of iron accumulation. 

Author Response

Point 1: the reviewer indicated the need for fine/minor spell check. We have gone over the manuscript to find these mistakes. 

Reviewer 2 Report

The topic of the review is very interesting and current.  The manuscript is well presented and well written and can be read with pleasure. The references cover the topic exhaustively.

Minor points:

lane 526 One reference is missing

lane 538-542 the requested information is missing

Author Response

Point 1: The reviewer indicated that a reference was missing on lane 526. Lanes 503-532 summarize a paper that has been accepted, but not yet published. The reference for this paper is on lane 532. The information for this reference is on lanes 812-813 which includes the information that we currently have for the reference. We felt that the information in this paper was particularly relevant to the topic of the review, and so we wished to include it.  

Point 2: The reviewer indicated that the information in lanes 538-542 were missing. We have added the information or indicated "N/A" when appropriate.