Is membrane homeostasis the missing link between inflammation and neurodegenerative diseases?

Natalia Sánchez De Groot,Marc Torrent Burgas

doi:10.1007/s00018-015-2038-4

Abstract

Systemic inflammation and infections are associated with neurodegenerative diseases. Unfortunately, the molecular bases of this link are still largely undiscovered. We, therefore, review how inflammatory processes can imbalance membrane homeostasis and theorize how this may have an effect on the aggregation behavior of the proteins implicated in such diseases. Specifically, we describe the processes that generate such imbalances at the molecular level, and try to understand how they affect protein folding and localization. Overall, current knowledge suggests that microglia pro-inflammatory mediators can generate membrane damage, which may have an impact in terms of triggering or accelerating disease manifestation.

Highlights

Neurodegenerative diseases are familial and sporadic conditions characterized by the progressive dysfunction of the nervous system [1, 2]
Current knowledge suggests that microglia pro-inflammatory mediators can generate membrane damage, which may have an impact in terms of triggering or accelerating disease manifestation
We review how inflammatory mechanisms can have an impact on membrane homeostasis and how this may perturb the key proteins associated with neurodegenerative disorders

Summary

Introduction

Neurodegenerative diseases are familial and sporadic conditions characterized by the progressive dysfunction of the nervous system [1, 2]. The origins of these diseases can be related to destabilizing mutations in proteins, which become less stable and more prone to aggregating or interacting with undesired partners [3]. In these examples, neurodegenerative conditions have a genetic, inheritable component and individuals develop them at an earlier age. It is widely recognized that such disorders are multifactorial and associated with both an individual genome and environmental conditions [7]. The molecules and signaling pathways involved in the inflammatory response have been widely characterized, it is still unclear how they influence the development of neurodegenerative diseases and are linked to environmental challenges. We review how inflammatory mechanisms can have an impact on membrane homeostasis and how this may perturb the key proteins associated with neurodegenerative disorders

Inflammation in neurodegenerative diseases

Inflammation in amyotrophic lateral sclerosis

Inflammation and membrane damage

Membrane perturbation in amyotrophic lateral sclerosis

Future perspectives