Protein Misfolding and Neurodegenerative Diseases

This special issue includes fifteen reviews and two original research articles by leading scientists in the fields of neu-ropathology, biochemistry, and cell biology, dealing with the role of protein aggregation and prion-like propagation of protein misfolding in neurodegenerative diseases. In the review article " Breaking the code of amyloid-í µí»½ oli-gomers, " available at the following link: Lesnè outlines the " oligomeric " view of the amyloid hypothesis in Alzheimer's disease (AD), discussing how structurally different amyloid-í µí»½ (Aí µí»½) oligomers may contribute to the pathogenesis, and the controversial role of the prion protein (PrP) in Aí µí»½ toxicity. He stresses the need to thoroughly characterize the oligomeric Aí µí»½ assemblies for dissecting the disease mechanisms and designing specific, effective therapies. Tau oligomers may also play an important neurotoxic role in AD. In the research article " Trimeric tau is toxic to human neuronal cells at low nanomolar concentrations, " available at the following link: nonphosphorylated human recombinant tau splice variants are neurotoxic at low nanomolar concentrations. They provide evidence that trimeric but not monomeric or dimeric tau is responsible for the toxicity. In the review article " The innate immune system in Alzheimer's disease , " available at the following link: A. Boutajangout and T. Wisniewski focus on the potential roles of the triggering receptor expressed on myeloid cells 2 protein (TREM2) and Toll-like receptors (TLRs) in AD. They give an overview of TREM2 functions and its involvement in phagocytic and anti-inflammatory pathways. They also review the critical roles of TLR4 and 9 in the innate immune response, the interplay of these pattern recognition receptors, and highlight the importance of microglia-mediated innate immunity in AD pathogenesis. Several articles deal with the cellular processes involved in protein folding and quality control and how their corruption may trigger neurotoxicity. In the review article " Disulfide bonding in neurodegenerative misfolding diseases, " available at the following link: discusses the role of disulfide bond formation; in the review article " Role of protein misfolding and proteostasis deficiency in protein misfolding diseases and aging, " available at the following link: Cuanalo-Contreras et al. review the involvement of the unfolded protein response (UPR), the ubiquitin proteasome system (UPS), autophagy, and aggresome formation in neu-rodegenerative diseases and aging. In the review article " ER dysfunction and protein folding stress in ALS, " available at the following link: on the role of UPR in amyotrophic lateral sclerosis …