Systemically targeting monocytic myloid-derrived suppressor cells using dendrimers and their cell-level biodistribution kinetics.

The focus of nanoparticles in vivo trafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalities in vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.

The effect of a bodybuilding carbohydrate-loading protocol on anthropometry: Preliminary findings from a randomized crossover trial.

To acutely enhance muscle size and definition, carbohydrate (CHO)-loading protocols are commonly implemented by bodybuilders in the week before competition. This study sought to evaluate the effects of a bodybuilding CHO-loading protocol on anthropometry. Four dieting males engaging in resistance training (RT) with very low body fat participated in this randomized crossover trial. Each experimental period consisted of data collection on days one, four, and five corresponding to baseline, postdepletion, and postloading phases, respectively. During depletion, a standardized RT regimen and diet was followed. This diet was maintained on day 4 with the addition of placebo (PLA) or CHO drinks which contained 9 g/kg BM CHO for postloading data collection on day 5. Body mass (BM), skinfold thickness (SF), and ultrasound muscle thickness (MT) were obtained with descriptive data at both group and individual level calculated. From baseline, BM, SF, and MT mostly decreased in both conditions following depletion. All outcomes then increased from postdepletion following CHO-loading (BM: +0.8%, SF: +1.1%, MT: +2.9%) but not with PLA. Comparing to baseline, postloading changes were greater with CHO (BM: +0.3%, SF: -2.3%, MT: +2.1%) than PLA (BM: -0.9%, SF: -0.5%, MT: -0.8%). Individual differences in response to each phase were also observed. Group level changes seemingly favor CHO-loading; however, it is difficult to judge whether these changes are practically meaningful as they may not be large enough to exceed measurement error and daily biological fluctuations. Before implementation, coaches and competitors should consider individualizing protocols through precompetition testing and visually assessing changes in physique.

A Survey of Resistance Training Practices Among Physique Competitors During Peak Week.

ABSTRACT: Homer, KA, Cross, MR, and Helms, ER. A survey of resistance training practices among physique competitors during peak week. J Strength Cond Res XX(X): 000-000, 2024-Physique athletes are ranked by their on-stage presentation of muscle size, proportionality, and leanness. To acutely maximize muscle size, competitors manipulate resistance training (RT) variables in the days before the contest, commonly referred to as peak week (PW). Resistance training manipulations during PW may act synergistically with nutrition strategies such as carbohydrate loading. However, because little information exists on changes made to RT during PW, the purpose of this research was to determine the current practices of physique athletes and whether competitor characteristics were predictive of the RT variables manipulated. A total of 104 responses to the RT section of a survey on PW nutrition and training were analyzed through a series of multiple logistic regression models to examine the relationship between RT manipulations and competitor characteristics. Furthermore, to determine the magnitude of differences between PW and the week before PW (WBPW) for these variables, a McNemar-Bowker test, paired t-tests, and Wilcoxon signed-rank tests were conducted for nominal, continuous, and discrete outcomes, respectively. For all statistical analyses, p <0.05 was deemed significant. Competitors generally adjusted RT in a variety of ways, where proximity-to-failure was the most frequently manipulated and training frequency was the least; however, no competitor characteristic predicted any of the RT variables manipulated. Within those who manipulated RT variables during PW, frequency, volume, and intensity decreased while repetition ranges of compound exercises increased, empirically confirming that competitors seek to reduce training stress during PW. Such findings can be incorporated in future experimental designs examining the efficacy of peaking strategies to enhance the generalizability of results.

Programmability and biomedical utility of intrinsically-disordered protein polymers.

Intrinsically disordered proteins (IDPs) exhibit molecular-level conformational dynamics that are functionally harnessed across a wide range of fascinating biological phenomena. The low sequence complexity of IDPs has led to the design and development of intrinsically-disordered protein polymers (IDPPs), a class of engineered repeat IDPs with stimuli-responsive properties. The perfect repetitive architecture of IDPPs allows for repeat-level encoding of tunable protein functionality. Designer IDPPs can be modeled on endogenous IDPs or engineered de novo as protein polymers with dual biophysical and biological functionality. Their properties can be rationally tailored to access enigmatic IDP biology and to create programmable smart biomaterials. With the goal of inspiring the bioengineering of multifunctional IDP-based materials, here we synthesize recent multidisciplinary progress in programming and exploiting the bio-functionality of IDPPs and IDPP-containing proteins. Collectively, expanding beyond the traditional sequence space of extracellular IDPs, emergent sequence-level control of IDPP functionality is fueling the bioengineering of self-assembling biomaterials, advanced drug delivery systems, tissue scaffolds, and biomolecular condensates -genetically encoded organelle-like structures. Looking forward, we emphasize open challenges and emerging opportunities, arguing that the intracellular behaviors of IDPPs represent a rich space for biomedical discovery and innovation. Combined with the intense focus on IDP biology, the growing landscape of IDPPs and their biomedical applications set the stage for the accelerated engineering of high-value biotechnologies and biomaterials.

An examination of the associations between nutritional peaking strategies in physique sport and competitor characteristics.

BACKGROUND: Physique athletes are subjectively judged on their on-stage esthetic per their competition division criteria. To succeed, competitors look to acutely enhance their appearance by manipulating nutritional variables in the days leading up to competition, commonly referred to as peak week (PW). Despite their documented wide adoption, PW strategies lack experimental evidence. Further, the relationship between the specific strategies and the characteristics of the competitors who implement them are unknown. The aim of this research was to examine the effect of competitor characteristics on the specific nutritional peaking strategies implemented, the length of these strategies, and the range of daily carbohydrate (CHO) intakes during these strategies. METHODS: A 58-item survey was developed to gather information on peak week nutrition and training practices of physique athletes. A total of 160 respondents above the age of 18 who had competed in the last 5 years completed the nutrition section. The topics analyzed for this paper included competitor demographics, peaking strategies utilized, and PW CHO intakes. Competitor demographics are presented with the use of descriptive statistics. Associations between competitor demographics and peaking strategies implemented, peaking strategy length, and daily CHO intake ranges were assessed using multiple logistic regression, multiple ordinal logistic regression, and linear mixed models, respectively. RESULTS: From the sampled population, ages 24-39 years (71.2%), male (68.8%), natural (65%), and amateur (90%) were the most common characteristics from their respective categories, while mean competition preparation length was 20.35 ± 8.03 weeks (Males: 19.77 ± 7.56 weeks, Females: 21.62 ± 8.93 weeks), competition preparation body mass loss was 11.5 ± 5.56 kg (M: 12.7 ± 5.76 kg, F: 7.16 ± 3.99 kg), and competition body mass was 72.09 ± 15.74 kg (M: 80.15 ± 11.33 kg, F: 54.34 ± 7.16 kg). For males, the highest and lowest daily CHO intake during PW were 489.63 ± 224.03 g (6.22 ± 2.93 g/kg body mass) and 148.64 ± 152.01 g (1.94 ± 2.17 g/kg), respectively, while for females these values were 266.73 ± 131.23 g (5.06 ± 2.67 g/kg) and 94.42 ± 80.72 g (1.81 ± 1.57 g/kg), respectively. CHO back loading (45%) and water loading (40.6%) were the most popular peaking strategies, while the most prevalent peaking strategy length was 7 days (27.2%). None of the competitor characteristics predicted the use of CHO-based peaking strategies nor peaking strategy length. For non-CHO-based strategies, drug-enhanced competitors were more likely to restrict water than non-drug enhanced, while males and professional competitors had greater odds of loading sodium than females and amateurs, respectively. Finally, when comparing the disparity in highest and lowest CHO intakes during peak week, sex was the only significant factor. CONCLUSIONS: The results of this survey provide further information on the nutritional peaking strategies implemented by competitors. Certain characteristics were identified as predictors of sodium loading and water restriction, and the range of daily PW CHO intake. Contrastingly, no associations were found for CHO-based peaking strategies or peaking strategy length. While our analyses may be underpowered, and thus results should be interpreted with caution, it appears the nutritional peaking strategies implemented by physique competitors are seemingly complex and highly individual.

Versatile Deep Learning Pipeline for Transferable Chemical Data Extraction.

Chemical information disseminated in scientific documents offers an untapped potential for deep learning-assisted insights and breakthroughs. Automated extraction efforts have shifted from resource-intensive manual extraction toward applying machine learning methods to streamline chemical data extraction. While current extraction models and pipelines have ushered in notable efficiency improvements, they often exhibit modest performance, compromising the accuracy of predictive models trained on extracted data. Further, current chemical pipelines lack both transferability─where a model trained on one task can be adapted to another relevant task with limited examples─and extensibility, which enables seamless adaptability for new extraction tasks. Addressing these gaps, we present ChemREL, a versatile chemical data extraction pipeline emphasizing performance, transferability, and extensibility. ChemREL utilizes a custom, diverse data set of chemical documents, labeled through an active learning strategy to extract two properties: normal melting point and lethal dose 50 (LD50). The normal melting point is selected for its prevalence in diverse contexts and wider literature, serving as the foundation for pipeline training. In contrast, LD50 evaluates the pipeline's transferability to an unrelated property, underscoring variance in its biological nature, toxicological context, and units, among other differences. With pretraining and fine-tuning, our pipeline outperforms existing methods and GPT-4, achieving F1-scores of 96.1% for entity identification and 97.0% for relation mapping, culminating in an overall F1-score of 95.4%. More importantly, ChemREL displays high transferability, effectively transitioning from melting point extraction to LD50 extraction with 10 randomly selected training documents. Released as an open-source package, ChemREL aims to broaden access to chemical data extraction, enabling the construction of expansive relational data sets that propel discovery.

Viral modulation of type II interferon increases T cell adhesion and virus spread.

During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread.

Promoting Photocatalytic Direct C-H Difluoromethylation of Heterocycles using Synergistic Dual-Active-Centered Covalent Organic Frameworks.

Difluoromethylation reactions are increasingly important for the creation of fluorine-containing heterocycles, which are core groups in a diverse range of biologically and pharmacologically active ingredients. Ideally, this typically challenging reaction could be performed photocatalytically under mild conditions. To achieve this separation of redox processes would be required for the efficient generation of difluoromethyl radicals and the reduction of oxygen. A covalent organic framework photocatalytic material was, therefore, designed with dual reactive centers. Here, anthracene was used as a reduction site and benzothiadiazole was used as an oxidation site, distributed in a tristyryl triazine framework. Efficient charge separation was ensured by the superior electron-donating and -accepting abilities of the dual centers, creating long-lived photogenerated electron-hole pairs. Photocatalytic difluoromethylation of 16 compounds with high yields and remarkable functional group tolerance was demonstrated; compounds included bioactive molecules such as xanthine and uracil. The structure-function relationship of the dual-active-center photocatalyst was investigated through electron spin resonance, femtosecond transient absorption spectroscopy, and density functional theory calculations.

Triazine Frameworks for the Photocatalytic Selective Oxidation of Toluene.

Investigations into the selective oxidation of inert sp3 C-H bonds using polymer photocatalysts under mild conditions have been limited. Additionally, the structure-activity relationship of photocatalysts often remains insufficiently explored. Here, a series of thiophene-based covalent triazine frameworks (CTFs) are used for the efficient and selective oxidation of hydrocarbons to aldehydes or ketones under ambient aerobic conditions. Spectroscopic methods conducted in situ and density functional theory (DFT) calculations revealed that the sulfur atoms within the thiophene units play a pivotal role as oxidation sites due to the generation of photogenerated holes. The effect of photogenerated holes on photocatalytic toluene oxidation was investigated by varying the length of the spacer in a CTF donor-acceptor based photocatalyst. Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG-579 using a photocatalytic protocol.

Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.

Peak Week Carbohydrate Manipulation Practices in Physique Athletes: A Narrative Review.

BACKGROUND: Physique athletes are ranked by a panel of judges against the judging criteria of the corresponding division. To enhance on-stage presentation and performance, competitors in certain categories (i.e. bodybuilding and classic physique) achieve extreme muscle size and definition aided by implementing acute "peaking protocols" in the days before competition. Such practices can involve manipulating nutrition and training variables to increase intramuscular glycogen and water while minimising the thickness of the subcutaneous layer. Carbohydrate manipulation is a prevalent strategy utilised to plausibly induce muscle glycogen supercompensation and subsequently increase muscle size. The relationship between carbohydrate intake and muscle glycogen saturation was first examined in endurance event performance and similar strategies have been adopted by physique athletes despite the distinct physiological dissimilarities and aims between the sports. OBJECTIVES: The aim of this narrative review is to (1) critically examine and appraise the existing scientific literature relating to carbohydrate manipulation practices in physique athletes prior to competition; (2) identify research gaps and provide direction for future studies; and (3) provide broad practical applications based on the findings and physiological reasoning for coaches and competitors. FINDINGS: The findings of this review indicate that carbohydrate manipulation practices are prevalent amongst physique athletes despite a paucity of experimental evidence demonstrating the efficacy of such strategies on physique performance. Competitors have also been observed to manipulate water and electrolytes in conjunction with carbohydrate predicated on speculative physiological mechanisms which may be detrimental for performance. CONCLUSIONS: Further experimental evidence which closely replicates the nutritional and training practices of physique athletes during peak week is required to make conclusions on the efficacy of carbohydrate manipulation strategies. Quasi-experimental designs may be a feasible alternative to randomised controlled trials to examine such strategies due to the difficulty in recruiting the population of interest. Finally, we recommend that coaches and competitors manipulate as few variables as possible, and experiment with different magnitudes of carbohydrate loads in advance of competition if implementing a peaking strategy.

Emerging conjugated polymers for heterogeneous photocatalytic chemical transformation.

In recent decades, the efficient utilization of solar energy through heterogeneous photocatalytic chemical transformation has attracted much attention. As emerging metal-free, pure organic and heterogeneous photocatalysts, π-conjugated polymers (CPs) have been used in visible-light-driven chemical transformations due to their stability, high specific surface area, metal-free nature, and high structural designability. In this review, we summarize the synthesis protocols and design strategies for efficient CP-based photocatalysts based on the photocatalytic mechanisms. Then we highlight the key progress in light-driven chemical transformation using CPs developed by our group. Finally, we present the outlook and possible challenges for future progress of the field.

Viral modulation of type II interferon increases T cell adhesion and virus spread.

During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expression of cytokines, including interferons (IFNs) which partly limit primary infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. How VZV infects lymphocytes from epithelial cells while evading the cytokine response has not been fully established. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity. Transcriptomic analysis revealed that gC in combination with IFN-γ increased the expression of a small subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), as well as several chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of epithelial cells resulted in lymphocyte function-associated antigen 1 (LFA-1)-dependent T cell adhesion. This gC activity required a stable interaction with IFN-γ and signalling through the IFN-γ receptor. Finally, the presence of gC during infection increased VZV spread from epithelial cells to peripheral blood mononuclear cells. This constitutes the discovery of a novel strategy to modulate the activity of IFN-γ, inducing the expression of a subset of ISGs, leading to enhanced T cell adhesion and virus spread.

Colonization of peripheral ganglia by herpes simplex virus type 1 and 2.

Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) infect and establish latency in neurons of the peripheral nervous system to persist lifelong in the host and to cause recurrent disease. During primary infection, HSV replicates in epithelial cells in the mucosa and skin and then infects neurites, highly dynamic structures that grow or retract in the presence of attracting or repelling cues, respectively. Following retrograde transport in neurites, HSV establishes latency in the neuronal nucleus. Viral and cellular proteins participate in the chromatinization of the HSV genome that regulates gene expression, persistence, and reactivation. HSV-2 modulates neurite outgrowth during primary infection and upon reactivation, probably to facilitate infection and survival of neurons. Whether HSV-1 modulates neurite outgrowth and the underlying mechanism is currently under investigation. This review deals with HSV-1 and HSV-2 colonization of peripheral neurons, with a focus on the modulation of neurite outgrowth by these viruses.

Emerging covalent triazine framework-based nanomaterials for electrochemical energy storage and conversion.

Recently, the increasing concerns regarding environmental and energy-related issues due to the use of fossil fuels have triggered extensive research on sustainable electrochemical energy storage and conversion (EESC). In this case, covalent triazine frameworks (CTFs) possess a large surface area, tailorable conjugated structures, electron donating-accepting/conducting moieties, and excellent chemical and thermal stabilities. These merits make them leading candidates for EESC. However, their poor electrical conductivity impedes electron and ion conduction, leading to unsatisfactory electrochemical performances, which limit their commercial applications. Thus, to overcome these challenges, CTF-based nanocomposites and their derivatives such as heteroatom-doped porous carbons, which inherit most of the merits of pristine CTFs, lead to excellent performances in the field of EESC. In this review, initially, we briefly highlight the existing strategies for the synthesis of CTFs with application-targeted properties. Next, we review the contemporary progress of CTFs and their derivatives related to electrochemical energy storage (supercapacitors, alkali-ion batteries, lithium-sulfur batteries, etc.) and conversion (oxygen reduction/evolution reaction, hydrogen evolution reaction, carbon dioxide reduction reaction, etc.). Finally, we discuss perspectives on current challenges and recommendations for the further development of CTF-based nanomaterials in burgeoning EESC research.

Direct Synthesis of 1-Butanol with High Faradaic Efficiency from CO2 Utilizing Cascade Catalysis at a Ni-Enhanced (Cr2O3)3Ga2O3 Electrocatalyst.

Electrochemical transformation of CO2 into energy-dense liquid fuels provides a viable solution to challenges regarding climate change and nonrenewable resource dependence. Here, we report on the modification of a Cr-Ga oxide electrocatalyst through the introduction of nickel to generate a catalyst that generates 1-butanol at unprecedented faradaic efficiencies (ξ = 42%). This faradaic efficiency occurs at -1.48 V vs Ag/AgCl, with 1-butanol production commencing at an overpotential of 320 mV. At this potential, minor products include formate, methanol, acetic acid, acetone, and 3-hydroxybutanal. At -1.0 and -1.4 V, 3-hydroxybutanal becomes the primary product. This is in contrast to the nickel-free (Cr2O3)3(Ga2O3) system, where neither 3-hydroxybutanal nor 1-butanol was detected. Mechanistic studies show that formate is the initial CO2 reduction product and identify acetaldehyde as the key intermediate. Nickel is found responsible for the coupling and reduction of acetaldehyde to generate the higher molecular weight carbon products observed. To the best of our knowledge, this is the first electrocatalyst to generate 1-butanol with high faradaic efficiency.

Dual Molecular Oxygen Activation Sites on Conjugated Microporous Polymers for Enhanced Photocatalytic Formation of Benzothiazoles.

Oxidative formation of high value compounds involving active oxygen species using heterogeneous polymeric photocatalysts has become a useful tool in catalysis. Controlling the interaction between the active sites on polymer photocatalysts and oxygen molecules is still challenging due to the rather large polymer backbone structure. Here, we design a triazine-containing donor acceptor-type conjugated microporous polymer (CMP) containing dual major active sites at F and N atoms for molecular oxygen activation. Introducing fluorine atoms on the CMP backbone led to a combined effect of enhanced adsorption and electron transfer of oxygen. Time-resolved photoluminescence, electronic paramagnetic resonance spectra, and DFT calculation revealed favorable absorption energy and electron transfer kinetics between the CMP and oxygen molecules, thus efficiently generating superoxide radicals (O2•-) and singlet oxygen (1O2) as main active oxygen species. The photocatalytic activity, selectivity, and reusability of the CMP was demonstrated by the photocatalytic formation of a variety of benzothiazoles.

Visible-Light-Promoted Switchable Selective Oxidations of Styrene Over Covalent Triazine Frameworks in Water.

Using photocatalytic oxidation to convert basic chemicals into high value compounds in environmentally benign reaction media is a current focus in catalytic research. The challenge lies in gaining controllability over product formation selectivity. We design covalent triazine frameworks as heterogeneous, metal-free, and recyclable photocatalysts for visible-light-driven switchable selective oxidation of styrene in pure water. Selectivity in product formation was achieved by activation or deactivation of the specific photogenerated oxygen species. Using the same photocatalyst, by deactivation of photogenerated H2 O2 , benzaldehyde was obtained with over 99 % conversion and over 99 % selectivity as a single product. The highly challenging and sensitive epoxidation of styrene was carried out by creating peroxymonocarbonate as an initial epoxidation agent in the presence of bicarbonate, which led to formation of styrene oxide with a selectivity up to 76 % with near quantitative conversion. This study demonstrates a preliminary yet interesting example for simple control over switchable product formation selectivity for challenging oxidation reactions of organic compounds in pure water.

Innate immune response to SARS-1 CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the {beta} strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon {lambda}1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and -synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and {beta}-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS.