Correction: Cell Therapy: A Safe and Efficacious Therapeutic Treatment for Alzheimer's Disease in APP+PS1 Mice.

[This corrects the article DOI: 10.1371/journal.pone.0049468.].

Alzheimer's Disease Immunotherapy: Current Strategies and Future Prospects.

Alzheimer's disease (AD) is an extremely complex and heterogeneous pathology influenced by many factors contributing to its onset and progression, including aging, amyloid-beta (Aß) plaques, tau fibril accumulation, inflammation, etc. Despite promising advances in drug development, there is no cure for AD. Although there have been substantial advancements in understanding the pathogenesis of AD, there have been over 200 unsuccessful clinical trials in the past decade. In recent years, immunotherapies have been at the forefront of these efforts. Immunotherapy alludes to the immunological field that strives to identify disease treatments via the enhancement, suppression, or induction of immune responses. Interestingly, immunotherapy in AD is a relatively new approach for non-infectious disease. At present, antibody therapy (passive immunotherapy) that targets anti-Aß aimed to prevent the fibrillization of Aß peptides and disrupt pre-existing fibrils is a predominant AD immunotherapy due to the continuous failure of active immunotherapy for AD. The most rational and safe strategies will be those targeting the toxic molecule without triggering an abnormal immune response, offering therapeutic advantages, thus making clinical trial design more efficient. This review offers a concise overview of immunotherapeutic strategies, including active and passive immunotherapy for AD. Our review encompasses approved methods and those presently under investigation in clinical trials, while elucidating the recent challenges, complications, successes, and potential treatments. Thus, immunotherapies targeting Aß throughout the disease progression using a mutant oligomer-Aß stimulated dendritic cell vaccine may offer a promising therapy in AD.

Antimicrobial Guanidinylate Polycarbonates Show Oral In Vivo Efficacy Against Clostridioides Difficile.

The emerging antibiotic resistance has been named by the World Health Organization (WHO) as one of the top 10 threats to public health. Notably, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF) are designated as serious threats, whereas Clostridioides difficile (C. difficile) is recognized as one of the most urgent threats to human health and unmet medical need. Herein, they report the design and application of novel biodegradable polymers - the lipidated antimicrobial guanidinylate polycarbonates. These polymers showed potent antimicrobial activity against a panel of bacteria with fast-killing kinetics and low resistance development tendency, mainly due to their bacterial membrane disruption mechanism. More importantly, the optimal polymer showed excellent antibacterial activity against C. difficile infection (CDI) in vivo via oral administration. In addition, compared with vancomycin, the polymer demonstrated a much-prolonged therapeutic effect and virtually diminished recurrence rate of CDI. The convenient synthesis, easy scale-up, low cost, as well as biodegradability of this class of polycarbonates, together with their in vitro broad-spectrum antimicrobial activity and orally in vivo efficacy against CDI, suggest the great potential of lipidated guandinylate polycarbonates as a new class of antibacterial biomaterials to treat CDI and combat emerging antibiotic resistance.

Helical sulfonyl-γ-AApeptides modulating Aß oligomerization and cytotoxicity by recognizing Aß helix.

In contrast to prevalent strategies which make use of ß-sheet mimetics to block Aß fibrillar growth, in this study, we designed a series of sulfonyl-γ-AApeptide helices that targeted the crucial α-helix domain of Aß13-26 and stabilized Aß conformation to avoid forming the neurotoxic Aß oligomeric ß-sheets. Biophysical assays such as amyloid kinetics and TEM demonstrated that the Aß oligomerization and fibrillation could be greatly prevented and even reversed in the presence of sulfonyl-γ-AApeptides in a sequence-specific and dose-dependent manner. The studies based on circular dichroism, Two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) spectra unambiguously suggested that the sulfonyl-γ-AApeptide Ab-6 could bind to the central region of Aß42 and induce α-helix conformation in Aß. Additionally, Electrospray ionisation-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) was employed to rule out a colloidal mechanism of inhibitor and clearly supported the capability of Ab-6 for inhibiting the formation of Aß aggregated forms. Furthermore, Ab-6 could rescue neuroblastoma cells by eradicating Aß-mediated cytotoxicity even in the presence of pre-formed Aß aggregates. The confocal microscopy demonstrated that Ab-6 could still specifically bind Aß42 and colocalize into mitochondria in the cellular environment, suggesting the rescue of cell viability might be due to the protection of mitochondrial function otherwise impaired by Aß42 aggregation. Taken together, our studies indicated that sulfonyl-γ-AApeptides as helical peptidomimetics could direct Aß into the off-pathway helical secondary structure, thereby preventing the formation of Aß oligomerization, fibrillation and rescuing Aß induced cell cytotoxicity.

Transcranial Electromagnetic Wave Treatment: A Fountain of Healthy Longevity?

Most diseases of older age have as their common denominator a dysfunctional immune system, wherein a low, chronic level of inflammation is present due to an imbalance of pro-inflammatory cytokines over anti-inflammatory cytokines that develops during aging ("inflamm-aging"). A gerotherapeutic that can restore the immune balance to that shared by young/middle-aged adults and many centenarians could reduce the risk of those age-related diseases and increase healthy longevity. In this perspectives paper, we discuss potential longevity interventions that are being evaluated and compare them to a novel gerotherapeutic currently being evaluated in humans-Transcranial Electromagnetic Wave Treatment (TEMT). TEMT is provided non-invasively and safety through a novel bioengineered medical device-the MemorEM-that allows for near complete mobility during in-home treatments. Daily TEMT to mild/moderate Alzheimer's Disease (AD) patients over a 2-month period rebalanced 11 of 12 cytokines in blood back to that of normal aged adults. A very similar TEMT-induced rebalancing of cytokines occurred in the CSF/brain for essentially all seven measurable cytokines. Overall inflammation in both blood and brain was dramatically reduced by TEMT over a 14-27 month period, as measured by C-Reactive Protein. In these same AD patients, a reversal of cognitive impairment was observed at 2 months into treatment, while cognitive decline was stopped over a 2½ year period of TEMT. Since most age-related diseases have the commonality of immune imbalance, it is reasonable to postulate that TEMT could rebalance the immune system in many age-related diseases as it appears to do in AD. We propose that TEMT has the potential to reduce the risk/severity of age-related diseases by rejuvenating the immune system to a younger age, resulting in reduced brain/body inflammation and a substantial increase in healthy longevity.

Short, Lipidated Dendrimeric γ-AApeptides as New Antimicrobial Peptidomimetics.

Antibiotic resistance is one of the most significant issues encountered in global health. There is an urgent demand for the development of a new generation of antibiotic agents combating the emergence of drug resistance. In this article, we reported the design of lipidated dendrimeric γ-AApeptides as a new class of antimicrobial agents. These AApeptides showed excellent potency and broad-spectrum activity against both Gram-positive bacteria and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The mechanistic studies revealed that the dendrimeric AApeptides could kill bacteria rapidly through the permeabilization of bacterial membranes, analogous to host-defense peptides (HDPs). These dendrimers also did not induce antibiotic resistance readily. The easy access to the synthesis, together with their potent and broad-spectrum activity, make these lipidated dendrimeric γ-AApeptides a new generation of antibacterial agents.

Multi-Targeting Intranasal Nanoformulation as a Therapeutic for Alzheimer's Disease.

Melatonin, insulin, and Δ9-tetrahydrocannabinol (THC) have been shown to reverse cognitive deficits and attenuate neuropathologies in transgenic mouse models of Alzheimer's disease (AD) when used individually. Here, we evaluated the therapeutic properties of long-term intranasal treatment with a novel nanoformulation containing melatonin, insulin, and THC in aged APPswe/PS1ΔE9 (APP/PS1) mice, a transgenic model of AD. Transgenic mice at the age of 12 months were intranasally administered with a new nanoformulation containing melatonin, insulin, and THC at doses of 0.04, 0.008, and 0.02 mg/kg, respectively, once daily for 3 months. The spatial memory of the mice was assessed using the radial arm water maze (RAWM) test before and after drug treatment. Brain tissues were collected at the end of the treatment period for the assessment of Aß load, tauopathy state, and markers of mitochondrial function. The RAWM test revealed that the treatment with the melatonin-insulin-THC (MIT) nasal spray improved the spatial learning memory of APP/PS1 mice significantly. Results of protein analyses of brain homogenates indicated that MIT treatment significantly decreased the tau phosphorylation implicated in tau toxicity (p < 0.05) and the expression of CKMT1 associated with mitochondrial dysfunction. Moreover, MIT significantly decreased the expression of two mitochondrial fusion-related proteins, Mfn2 and Opa1 (p < 0.01 for both), while increasing the expression of a mitophagy regulator, Parkin, suggesting a compensatory enhancement of mitophagy due to MIT-promoted mitochondrial fusion. In conclusion, this study was the first to demonstrate the ability of an MIT nanoformulation to improve spatial memory in AD mice through its multi-targeting effects on Aß production, tau phosphorylation, and mitochondrial dynamics. Thus, MIT may be a safe and effective therapeutic for AD.

Development of lipidated polycarbonates with broad-spectrum antimicrobial activity.

Antimicrobial resistance is a global challenge owing to the lack of discovering effective antibiotic agents. Antimicrobial polymers containing the cationic groups and hydrophobic groups which mimic natural host-defense peptides (HDPs) show great promise in combating bacteria. Herein, we report the synthesis of lipidated polycarbonates bearing primary amino groups and hydrophobic moieties (including both the terminal long alkyl chain and hydrophobic groups in the sequences) by ring-opening polymerization. The hydrophobic/hydrophilic group ratios were adjusted deliberately and the lengths of the alkyl chains at the end of the polymers were modified to achieve the optimized combination for the lead polymers, which exhibited potent and broad-spectrum bactericidal activity against a panel of Gram-positive and Gram-negative bacteria. The polymers only showed very limited hemolytic activity, demonstrating their excellent selectivity. Comprehensive analyses using biochemical and biophysical assays revealed the strong interaction between the polymers and bacteria membranes. Moreover, the polymers also showed strong biofilm inhibition activity and did not readily induce antibiotic resistance. Our results suggest that lipidated polycarbonates could be a new class of antimicrobial agents.

Expression level comparison of marker genes related to early embryonic development and tumor growth.

In tumor research, the occurrence and origin of tumors are the fundamental problems. In the 1970s, the basic discussion of the developmental biology problem of tumors was proposed, and it was believed that tumorigenesis is closely related to developmental biology. Tumors are abnormal biological structures in organisms, and their biological behavior is very similar to that of the early embryo. Many tumor-related genes also serve regulatory roles in the normal development and differentiation of embryos. However, it remains unclear whether gene expression in early embryos has any similarities with tumor cells. In this study, to compare the similarities and differences in gene expression between early embryos and tumor cells, reverse transcription-quantitative PCR was conducted to determine and compare the relative expression levels of nine tumor-related genes in the brain glioma cell line, T98G, and in the early embryo of Spodoptera litura, which is fast-growing, low-cost, easily accessible and easy to observe. The expression of tumor-related genes in early embryos and the similarity of regulatory mechanisms between early embryonic development and tumor growth were explored. In conclusion, tumor growth may be regarded as an abnormal embryogenic activation that happens in the organs of adult individuals.

A novel cyclic γ-AApeptide-based long-acting pan-coronavirus fusion inhibitor with potential oral bioavailability by targeting two sites in spike protein.

The receptor-binding domain (RBD) in S1 subunit and heptad repeat 1 (HR1) domain in S2 subunit of SARS-CoV-2 spike (S) protein are the targets of neutralizing antibodies (nAbs) and pan-coronavirus (CoV) fusion inhibitory peptides, respectively. However, neither nAb- nor peptide-based drugs can be used orally. In this study, we screened a one-bead-two-compound (OBTC) cyclic γ-AApeptide library against SARS-CoV-2 S protein and identified a hit: S-20 with potent membrane fusion inhibitory activity, but moderate selectivity index (SI). After modification, one derivative, S-20-1, exhibited improved fusion inhibitory activity and SI (>1000). S-20-1 could effectively inhibit infection by pseudotyped and authentic SARS-CoV-2 and pseudotyped variants of concern (VOCs), including B.1.617.2 (Delta) and B.1.1.529 (Omicron), as well as MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. It could also inhibit infection of a pseudotyped SARS-related coronavirus WIV1 (SARSr-CoV-WIV1) from bats. Intranasal application of S-20-1 to mice before or after challenge with HCoV-OC43 or SARS-CoV-2 provided significant protection from infection. Importantly, S-20-1 was highly resistant to proteolytic degradation, had long half-life, and possessed favorable oral bioavailability. Mechanistic studies suggest that S-20-1 binds with high affinity to RBD in S1 and HR1 domain in S2 of SARS-CoV-2 S protein. Thus, with its pan-CoV fusion and entry inhibitory activity by targeting two sites in S protein, desirable half-life, and promising oral bioavailability, S-20-1 is a potential candidate for further development as a novel therapeutic and prophylactic drug against infection by SARS-CoV-2 and its variants, as well as future emerging and reemerging CoVs.

The Immune System as a Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of AD treatments, setbacks have been more prominent than successes. Recent studies have shown that there is an intricate connection between the immune and central nervous systems, which can be imbalanced and thereby mediate neuroinflammation and AD. Thus, this review examines this connection and how it can be altered with AD. Recent developments in active and passive immunotherapy for AD are also discussed as well as suggestions for improving these therapies moving forward.

Transcranial Electromagnetic Treatment Stops Alzheimer's Disease Cognitive Decline over a 2½-Year Period: A Pilot Study.

Background: There is currently no therapeutic that can stop or reverse the progressive memory impairment of Alzheimer's disease (AD). However, we recently published that 2 months of daily, in-home transcranial electromagnetic treatment (TEMT) reversed the cognitive impairment in eight mild/moderate AD subjects. These cognitive enhancements were accompanied by predicted changes in AD markers within both the blood and cerebrospinal fluid (CSF). Methods: In view of these encouraging findings, the initial clinical study was extended twice to encompass a period of 2½ years. The present study reports on the resulting long-term safety, cognitive assessments, and AD marker evaluations from the five subjects who received long-term treatment. Results: TEMT administration was completely safe over the 2½-year period, with no deleterious side effects. In six cognitive/functional tasks (including the ADAS-cog13, Rey AVLT, MMSE, and ADL), no decline in any measure occurred over this 2½-year period. Long-term TEMT induced reductions in the CSF levels of C-reactive protein, p-tau217, Aß1-40, and Aß1-42 while modulating CSF oligomeric Aß levels. In the plasma, long-term TEMT modulated/rebalanced levels of both p-tau217 and total tau. Conclusions: Although only a limited number of AD patients were involved in this study, the results suggest that TEMT can stop the cognitive decline of AD over a period of at least 2½ years and can do so with no safety issues.

Transcranial Electromagnetic Treatment "Rebalances" Blood and Brain Cytokine Levels in Alzheimer's Patients: A New Mechanism for Reversal of Their Cognitive Impairment.

Background: The immune system plays a critical role in the development and progression of Alzheimer's disease (AD). However, there is disagreement as to whether development/progression of AD involves an over-activation or an under-activation of the immune system. In either scenario, the immune system's cytokine levels are abnormal in AD and in need of rebalancing. We have recently published a pilot clinical trial (https://clinicaltrials.gov/ct2/show/NCT02958930) showing that 2 months of daily in-home Transcranial Electromagnetic Treatment (TEMT) was completely safe and resulted in reversal of AD cognitive impairment. Methods: For the eight mild/moderate AD subjects in this published work, the present study sought to determine if their TEMT administration had immunologic effects on blood or CSF levels of 12 cytokines. Subjects were given daily in-home TEMT for 2 months by their caregivers, utilizing first-in-class MemorEM™ devices. Results: For eight plasma cytokines, AD subjects with lower baseline cytokine levels always showed increases in those cytokines after both a single treatment or after 2-months of daily TEMT. By contrast, those AD subjects with higher baseline cytokine levels in plasma showed treatment-induced decreases in plasma cytokines at both time points. Thus, a gravitation to reported normal plasma cytokine levels (i.e., a "rebalancing") occurred with both acute and long-term TEMT. In the CSF, TEMT-induced a similar rebalancing for seven measurable cytokines, the direction and extent of changes in individual subjects also being linked to their baseline CSF levels. Conclusion: Our results strongly suggest that daily TEMT to AD subjects for 2-months can "rebalance" levels for 11 of 12 cytokines in blood and/or brain, which is associated with reversal of their cognitive impairment. TEMT is likely to be providing these immunoregulatory effects by affecting cytokine secretion from: (1) blood cells traveling through the head's vasculature, and (2) the brain's microglia/astrocytes, choroid plexus, or neurons. This rebalancing of so many cytokines, and in both brain and systemic compartments, appears to be a remarkable new mechanism of TEMT action that may contribute substantially to it's potential to prevent, stop, or reverse AD and other diseases of aging.

The Memory Benefit to Aged APP/PS1 Mice from Long-Term Intranasal Treatment of Low-Dose THC.

THC has been used as a promising treatment approach for neurological disorders, but the highly psychoactive effects have largely warned off many scientists from pursuing it further. We conducted an intranasal treatment using low-dose THC on 12-month-old APP/PS1 mice daily for 3 months to overcome any potential psychoactive response induced by the systemic delivery. Our results demonstrate that the THC nasal treatment at 0.002 and 0.02 mg/kg significantly slowed the memory decline compared to that in the vehicle-treated transgenic mouse control group. An enzyme-linked immunosorbent assay showed that the Aß1-40 and 1-42 peptides decreased in the THC-treated groups. The Western blot data indicate that long-term low-dose THC intranasal administration promoted p-tau level reduction and mitochondrial function marker redistribution. The blood biochemical parameter data demonstrate some insignificant changes in cytokine, immunoglobulin, and immune cell profiles during intranasal THC treatment. Intranasal delivery is a non-invasive and convenient method that rapidly targets therapeutics to the brain, minimizing systemic exposure to avoid unwanted adverse effects. Our study provides new insights into the role of low-dose THC intranasal treatment as a pharmacological strategy to counteract alterations in Alzheimer's disease-related cognitive performance.

Commercial and Instant Coffees Effectively Lower Aß1-40 and Aß1-42 in N2a/APPswe Cells.

Background: Alzheimer's disease (AD) is a multifactorial neurological disease with neurofibrillary tangles and neuritic plaques as histopathological markers. Due to this, although AD is the leading cause of dementia worldwide, clinical AD dementia cannot be certainly diagnosed until neuropathological post-mortem evaluation. Coffee has been reported to have neurologically protective factors, particularly against AD, but coffee brand and type have not been taken into consideration in previous studies. We examined the discrepancies among popular commercial and instant coffees in limiting the development and progression through Aß1-40 and Aß1-42 production, and hypothesized that coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of Aß-related AD. Methods: Coffee samples from four commercial coffee brands and four instant coffees were purchased or prepared following given instructions and filtered for the study. 5, 2.5, and 1.25% concentrations of each coffee were used to treat N2a/APPswe cell lines. MTT assay was used to assess cell viability for coffee concentrations, as well as pure caffeine concentrations. Sandwich ELISA assay was used to determine Aß concentration for Aß1-40 and Aß1-42 peptides of coffee-treated cells. Results: Caffeine concentrations were significantly varied among all coffees (DC vs. MDC, PC, SB, NIN, MIN p < 0.05). There was no correlation between caffeine concentration and cell toxicity among brands and types of coffee, with no toxicity at 0.5 mg/ml caffeine and lower. Most coffees were toxic to N2a/APPswe cells at 5% (p < 0.05), but not at 2.5%. Most coffees at a 2.5% concentration reduced Aß1-40 and Aß1-42 production, with comparable results between commercial and instant coffees. Conclusion: All coffees tested have beneficial health effects for AD through lowering Aß1-40 and Aß1-42 production, with Dunkin' Donuts® medium roast coffee demonstrating the most consistent and optimal cell survival rates and Aß concentration. On the other hand, Starbucks® coffee exhibited the highest cell toxicity rates among the tested coffees.

The Multifaceted Role of Neuroprotective Plants in Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder characterized by impaired cognition, memory loss, and altered personality. Many of the available pharmaceutical treatments do not alter the onset of disease progression. Recently, alternatives to developed drug candidates have been explored including medicinal plants and herbal treatments for the treatment of AD. This article examines the role of herbal plant extracts and the neuroprotective effects as alternative modes of intervention for AD progression. These extracts contain key metabolites that culminate alterations in AD progression. The traditional plant extracts explored in this article induce a variety of beneficial properties, including antioxidants, anti-inflammatory, and enhanced cognition, while also inducing activity on AD drug targets such as Aß degradation. While these neuroprotective aspects for AD are relatively recent, there is great potential in the drug discovery aspect of these plant extracts for future use in AD treatment.

Developing an Effective Peptide-Based Vaccine for COVID-19: Preliminary Studies in Mice Models.

Coronavirus disease 2019 (COVID-19) has caused massive health and economic disasters worldwide. Although several vaccines have effectively slowed the spread of the virus, their long-term protection and effectiveness against viral variants are still uncertain. To address these potential shortcomings, this study proposes a peptide-based vaccine to prevent COVID-19. A total of 15 B cell epitopes of the wild-type severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein were selected, and their HLA affinities predicted in silico. Peptides were divided into two groups and tested in C57BL/6 mice with either QS21 or Al(OH)3 as the adjuvant. Our results demonstrated that the peptide-based vaccine stimulated high and durable antibody responses in mice, with the T and B cell responses differing based on the type of adjuvant employed. Using epitope mapping, we showed that our peptide-based vaccine produced antibody patterns similar to those in COVID-19 convalescent individuals. Moreover, plasma from vaccinated mice and recovered COVID-19 humans had the same neutralizing activity when tested with a pseudo particle assay. Our data indicate that this adjuvant peptide-based vaccine can generate sustainable and effective B and T cell responses. Thus, we believe that our peptide-based vaccine can be a safe and effective vaccine against COVID-19, particularly because of the flexibility of including new peptides to prevent emerging SARS-CoV-2 variants and avoiding unwanted autoimmune responses.

Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice.

Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer's disease (AD) have been sparse due to the concern about THC's psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models. The effect of THC on amyloid-ß (Aß) production was examined in N2a/AßPPswe cells. An in vivo study was conducted in aged APP/PS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mg/kg every other day for three months. The in vitro study showed that THC inhibited Aß aggregation within a safe dose range. Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mg/kg of THC for three months significantly improved the spatial learning performance of aged APP/PS1 mice in a dose-dependent manner. Results of protein analyses revealed that low-dose THC treatment significantly decreased the expression of Aß oligomers, phospho-tau and total tau, and increased the expression of Aß monomers and phospho-GSK-3ß (Ser9) in the THC-treated brain tissues. In conclusion, treatment with THC at 0.2 and 0.02 mg/kg improved the spatial learning of aged APP/PS1 mice, suggesting low-dose THC is a safe and effective treatment for AD.

Examining the Toxicity of α-Synuclein in Neurodegenerative Disorders.

α-synuclein is considered the main pathological protein in a variety of neurodegenerative disorders, such as Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. As of now, numerous studies have been aimed at examining the post-translational modifications of α-synuclein to determine their effects on α-synuclein aggregation, propagation, and oligomerization, as well as the potential cellular pathway dysfunctions caused by α-synuclein, to determine the role of the protein in disease progression. Furthermore, α-synuclein also appears to contribute to the fibrilization of tau and amyloid beta, which are crucial proteins in Alzheimer's disease, advocating for α-synuclein's preeminent role in neurodegeneration. Due to this, investigating the mechanisms of toxicity of α-synuclein in neurodegeneration may lead to a more proficient understanding of the timeline progression in neurodegenerative synucleinopathies and could thereby lead to the development of potent targeted therapies.

COVID-19 Vaccines: Current Conditions and Future Prospects.

It has been over a year since SARS-CoV-2 was first reported in December of 2019 in Wuhan, China. To curb the spread of the virus, many therapies and cures have been tested and developed, most notably mRNA and DNA vaccines. Federal health agencies (CDC, FDA) have approved emergency usage of these S gene-based vaccines with the intention of minimizing any further loss of lives and infections. It is crucial to assess which vaccines are the most efficacious by examining their effects on the immune system, and by providing considerations for new technological vaccine strategies in the future. This paper provides an overview of the current SARS-CoV-2 vaccines with their mechanisms of action, current technologies utilized in manufacturing of the vaccines, and limitations in this new field with emerging data. Although the most popular COVID-19 vaccines have been proven effective, time will be the main factor in dictating which vaccine will be able to best address mutations and future infection.