Neurodegenerative diseases comprise an array of progressive neurological disorders all characterized by the selective death of neurons in the central nervous system. Although, rare (familial) and common (sporadic) forms can occur for the same disease, it is unclear whether this reflects several distinct pathogenic pathways or the convergence of different causes into a common form of nerve cell death. Remarkably, neurodegenerative diseases are increasingly found to be accompanied by activation of the innate immune surveillance system normally associated with pathogen recognition and response. Innate surveillance is the cell's quality control system for the purpose of detecting such danger signals and responding in an appropriate manner. Innate surveillance is an “intelligent system,” in that the manner of response is relevant to the magnitude and duration of the threat. If possible, the threat is dealt with within the cell in which it is detected, by degrading the danger signal(s) and restoring homeostasis. If this is not successful then an inflammatory response is instigated that is aimed at restricting the spread of the threat by elevating degradative pathways, sensitizing neighboring cells, and recruiting specialized cell types to the site. If the danger signal persists, then the ultimate response can include not only the programmed cell death of the original cell, but the contents of this dead cell can also bring about the death of adjacent sensitized cells. These responses are clearly aimed at destroying the ability of the detected pathogen to propagate and spread. Innate surveillance comprises intracellular, extracellular, non-cell autonomous and systemic processes. Recent studies have revealed how multiple steps in these processes involve proteins that, through their mutation, have been linked to many familial forms of neurodegenerative disease. This suggests that individuals harboring these mutations may have an amplified response to innate-mediated damage in neural tissues, and renders innate surveillance mediated cell death a plausible common pathogenic pathway responsible for neurodegenerative diseases, in both familial and sporadic forms. Here we have assembled evidence in favor of the hypothesis that neurodegenerative disease is the cumulative result of chronic activation of the innate surveillance pathway, triggered by endogenous or environmental danger or damage associated molecular patterns in a progressively expanding cascade of inflammation, tissue damage and cell death.

Aging and age-related neurodegeneration are both associated with the accumulation of unfolded and abnormally folded proteins, highlighting the importance of protein homeostasis (termed proteostasis) in maintaining organismal health. To this end, two cellular compartments with essential protein folding functions, the endoplasmic reticulum (ER) and the mitochondria, are equipped with unique protein stress responses, known as the ER unfolded protein response (UPRER) and the mitochondrial UPR (UPRmt), respectively. These organellar UPRs play roles in shaping the cellular responses to proteostatic stress that occurs in aging and age-related neurodegeneration. The loss of adaptive UPRER and UPRmt signaling potency with age contributes to a feed-forward cycle of increasing protein stress and cellular dysfunction. Likewise, UPRER and UPRmt signaling is often altered in age-related neurodegenerative diseases; however, whether these changes counteract or contribute to the disease pathology appears to be context dependent. Intriguingly, altering organellar UPR signaling in animal models can reduce the pathological consequences of aging and neurodegeneration which has prompted clinical investigations of UPR signaling modulators as therapeutics. Here, we review the physiology of both the UPRER and the UPRmt, discuss how UPRER and UPRmt signaling changes in the context of aging and neurodegeneration, and highlight therapeutic strategies targeting the UPRER and UPRmt that may improve human health.

Rotylenchulus reniformis Linford & Oliveira is increasing in incidence in cotton‐growing areas throughout the southern USA east of New Mexico. Cotton (Gossypium hirsutum L.) cultivars resistant to R. reniformis are currently unavailable. Management depends on a crop sequence with nonhosts of the nematode. In South Texas, the sequence of cotton with grain sorghum [Sorghum bicolor (L.) Moench] or corn (Zea mays L.) has become a standard practice. To improve farm efficiency, the implementation of rotation crops that are economically superior to grain sorghum is desirable. Eighteen cultivars of soybean [Glycine max (L.) Merr.] were tested in nonfumigated and in fumigated sandy loam soil infested with R. reniformis to evaluate nematode resistance of soybean under field conditions. Shank application of 1,3‐dichloropropene at a 38‐cm depth reduced R. reniformis population densities at the 15‐ to 60‐cm depth compared with preseason counts. The effect of each soybean cultivar on the growth and yield of a subsequent cotton crop was compared with the impact of grain sorghum and fallow. High‐yielding cultivars of soybean (HY574, Padre, DP7375RR, and NK83‐30) with reniform nematode‐suppressing potential were identified among cultivars within maturity groups 5, 6, 7, and 8. In contrast, cotton yields following the susceptible cultivars Santa Rosa‐R, Vernal, and DP6880RR were on average 25% lower than those following grain sorghum. The enrichment of cotton sequences with reniform nematode‐resistant soybean cultivars is viable when the proper cultivars are chosen, whereas the use of reniform nematode‐susceptible soybean cultivars is discouraged. The effective use of R. reniformis‐resistant soybean cultivars to manage R. reniformis in cotton will depend on a number of additional economic parameters not studied in these experiments.

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