Pregnane X receptor reduces particulate matter-induced type 17 inflammation in atopic dermatitis.

Background: Epidemiological evidence suggests that particulate matter (PM) exposure can trigger or worsen atopic dermatitis (AD); however, the underlying mechanisms remain unclear. Recently, pregnane X receptor (PXR), a xenobiotic receptor, was reported to be related to skin inflammation in AD. Objectives: This study aimed to explore the effects of PM on AD and investigate the role of PXR in PM-exposed AD. Methods: In vivo and in vitro AD-like models were employed, using BALB/c mice, immortalized human keratinocytes (HaCaT), and mouse CD4 + T cells. Results: Topical application of PM significantly increased dermatitis score and skin thickness in AD-like mice. PM treatment increased the mRNA and protein levels of type 17 inflammatory mediators, including interleukin (IL)-17A, IL-23A, IL-1ß, and IL-6, in AD-like mice and human keratinocytes. PM also activated PXR signaling, and PXR knockdown exacerbated PM-induced type 17 inflammation in human keratinocytes and mouse CD4 + T cells. In contrast, PXR activation by rifampicin (a human PXR agonist) reduced PM-induced type 17 inflammation. Mechanistically, PXR activation led to a pronounced inhibition of the nuclear factor kappa B (NF-κB) pathway. Conclusion: In summary, PM exposure induces type 17 inflammation and PXR activation in AD. PXR activation reduces PM-induced type 17 inflammation by suppressing the NF-κB signaling pathway. Thus, PXR represents a promising therapeutic target for controlling the PM-induced AD aggravation.

Proteomic analysis of cardiovascular disease-associated proteins in Korean patients with moderate-to-severe atopic dermatitis.

Background: Cardiovascular diseases (CVDs) have been associated with atopic dermatitis (AD), including in Korean patients. Previous studies on AD have primarily focused on patients of European ancestry, while the Asian endotype exhibits distinct characteristics. This study aimed to characterize the blood proteomic signature of Korean patients with moderate-to-severe AD, with an emphasis on proteins related to CVDs. Methods: A total of 78 participants, including 39 patients with moderate-to-severe AD and 39 age- and sex-matched healthy controls, were enrolled. Blood proteomics analysis was performed using the Olink CVD II panel, which measures the expression levels of 92 proteins associated with CVDs. Results: Unsupervised hierarchical clustering revealed 44 upregulated and 5 downregulated proteins in AD patients compared to healthy controls. Principal component analysis (PCA) effectively distinguished AD patients from healthy subjects based on the complete set of proteins or the subset of upregulated proteins. A multiple linear regression model comprising CCL17 and FGF21 showed a strong correlation with disease severity (R = 0.619). Correlation analysis identified 25 highly correlated proteins, including STK4, ITGB1BP2, and DECR1, which were newly found to be upregulated in Korean AD patients. Pathway analysis highlighted the involvement of these proteins in vascular system, inflammation, and lipid metabolism pathways. Conclusion: The blood proteomic profile of moderate-to-severe AD patients in Korea differed from healthy controls using the CVD II panel. This study provides potential biomarkers for the AD-CVD association and insights into the pathways contributing to this relationship in the Korean population.

Skin Toxicities Induced by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and their Influence on Treatment Adjustments in Lung Cancer Patients.

Skin toxicities caused by epidermal growth factor receptor tyrosine kinase inhibitors can affect patient quality of life and lead to treatment adjustments, including dose reduction or discontinuation. This retrospective study aimed to profile skin toxicities and their impact on treatment adjustments. A total of 288 non-small cell lung cancer patients treated with first-, second-, or third-generation epidermal growth factor receptor tyrosine kinase inhibitors were included. Skin toxicities, including papulopustular rash, xerosis, paronychia, and pruritus, were assessed based on medical records, and their severity was evaluated based on the required dermatological intervention. Papulopustular rash was the most common toxicity (74.3%), followed by pruritus (61.1%), xerosis (52.4%), and paronychia (39.6%). Papulopustular rash was more common in males and more severe in younger patients. Papulopustular rash was more prevalent in patients treated with first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors, while paronychia was notably frequent for the second-generation epidermal growth factor receptor tyrosine kinase inhibitors. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors frequently caused multiple skin toxicities. Importantly, skin toxicities led to epidermal growth factor receptor tyrosine kinase inhibitor treatment adjustments in 26.7% of cases, with second-generation epidermal growth factor receptor tyrosine kinase inhibitors demonstrating higher adjustment rates. Papulopustular rash and paronychia were the main causes of treatment adjustments, with even mild paronychia being linked to treatment adjustments. Effective management of skin toxicities is essential for optimizing treatment outcomes in patients receiving epidermal growth factor receptor tyrosine kinase inhibitors.

Nevus Spilus, Partial Unilateral Lentiginosis, and Linear and Whorled Nevoid Hypermelanosis: A Comparison of Clinical Features, Course, and Treatment Response.

Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study's data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway.

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.

Mapping the immune cell landscape of severe atopic dermatitis by single-cell RNA-seq.

BACKGROUND: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. METHODS: Employing single-cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. RESULTS: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2-priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. CONCLUSION: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation.

The reporting quality of acupuncture-related traumatic adverse events: a systematic review of case studies in Korea.

BACKGROUND: Acupuncture is known for a harmless treatment when administered by well-trained clinicians. However, multiple case reports of traumatic adverse events (AEs) related to acupuncture treatments continue to be published in literature. In this review, we evaluated the reporting quality and conducted causality assessments of case studies that have reported acupuncture-related traumatic AEs in Korea. METHODS: Eight databases were searched from their inception to January 2024. Only Korean case studies that reported traumatic AEs following acupuncture procedures were included without any language restrictions. Reporting quality was evaluated based on patient characteristics, AEs, and acupuncture practice. Causality was assessed using the modified WHO-UMC causality criteria. RESULTS: Twenty-eight studies were included from a total of 1,154 identified studies. The quality of reporting in the included studies was low overall. While the descriptions of patient characteristics and AEs were relatively well detailed, most information on acupuncture practice was not reported at all. During the causality assessment, only three (10.7%) studies were judged to be "certain". Twelve (42.9%) studies were "unassessable" because they inadequately described the information necessary for decision-making. It was practically difficult to establish the causality between acupuncture and AEs, as well as the appropriateness of acupuncture practice. CONCLUSIONS: Insufficient and inappropriate reporting was observed in most case studies reporting acupuncture-related traumatic AEs in Korea. To overcome these limitations, we have suggested tentative guidelines in the form of a set of items that should be reported by future authors who plan to publish case studies on acupuncture-related traumatic AEs in a clinical setting.

Efficacy and safety of acupuncture treatment for fatigue after COVID-19 infection: study protocol for a pilot randomized sham-controlled trial.

Background: As the coronavirus disease 2019 (COVID-19) pandemic has spread globally, its sequelae, called Long COVID, have persisted, troubling patients worldwide. Although fatigue is known to be the most frequent among Long COVID symptoms, its mechanism and treatment have not been clearly demonstrated. In 2022, we conducted a preliminary prospective case series and found that acupuncture and moxibustion were feasible interventions for fatigue. This study is a pilot patient-assessor-blinded randomized sham-controlled trial to evaluate the efficacy and safety of acupuncture treatment for patients with fatigue that has persisted for at least 4 weeks after recovery from COVID-19. Methods: Thirty patients will be recruited and randomly assigned to either the acupuncture or sham acupuncture treatment groups. Treatment will be conducted thrice a week for both groups during 4 weeks. The primary outcome will be the efficacy and safety of acupuncture, including numeric rating scale (NRS), brief fatigue inventory (BFI), fatigue severity scale (FSS), and adverse event evaluation. Secondary outcomes will be evaluation of improvement in the comorbid symptoms of fatigue and feasibility variables. Outcome variables will be assessed before treatment, 4 weeks after treatment, and 8 weeks after treatment completion. Discussion: The results of this study will be used to clarify the efficacy and safety of acupuncture treatment for persistent fatigue in patients with Long COVID. Additionally, the feasibility of the study design was validated to provide evidence for future full-scale randomized controlled trials.Clinical trial registration: identifier: KCT0008656 https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24785&search_page=L.

A Study on the Monitoring of Toxocara spp. in Various Children's Play Facilities in the Republic of Korea (2016-2021).

Toxocara spp. is a zoonotic soil-transmitted parasite that infects canids and felids, which causes toxocariasis in humans, migrating to organ systems, including the lungs, the ocular system, and the central nervous system. Since Toxocara spp. is usually transmitted through soil, children tend to be more susceptible to infection. In order to monitor contamination with Toxocara spp. in children's play facilities in the Republic of Korea, we investigated 11,429 samples of soil from daycare centers, kindergartens, elementary schools, and parks across the country from January 2016 to December 2021. Since the Environmental Health Act in the Republic of Korea was enacted in March 2008, there have been sporadic reports of contamination by Toxocara spp. in children's activity zones. In this study, soil from children's play facilities in regions across the Republic of Korea was monitored according to the Korean standardized procedure to use it as basic data for preventive management and public health promotion. The national average positive rate was 0.16% (18/11,429), and Seoul showed a higher rate of 0.63% (2/318) than any other regions while Incheon, Daegu, Ulsan, Kangwon-do, Jeollabuk-do, and Jeollanam-do were negative (p < 0.05). The positive rates were as follows: 0.37% (4/1089) in daycare centers, 0.13% (3/2365) in kindergartens, 0.2% (7/4193) in elementary schools, 0.09% (1/1143) in apartments, and 0.14% (3/2198) in parks. In addition, it was confirmed that 0.2% (1/498) of elementary schools and 1.17% (2/171) of parks were re-contaminated among play facilities managed with the establishment of a regular inspection cycle. Consequently, there is an essential need for continuous monitoring of Toxocara spp. contamination and regular education for preschool and school children in order to prevent soil-borne parasite infections.

Perianal Pseudoverrucous Papules and Nodules in an Elderly Patient.

Pseudoverrucous papules and nodules is a reaction to irritation usually associated with urostomies. We report a case of perianal pseudoverrucous papules and nodules in an elderly patient who developed a characteristic diaper dermatitis after infrequent diaper change. The perianal papulonodular lesions improved after saline wet dressing and topical steroid application. These perianal pseudoverrucous papules and nodules indicate a unique type of irritant diaper dermatitis, which can be distinguished from Jacquet erosive diaper dermatitis and granuloma gluteale adultorum. Identifying this condition is important because pseudoverrucous papules and nodules can resemble more serious dermatoses, leading to unnecessary investigations being carried out.

Impact of ultraviolet radiation on cardiovascular and metabolic disorders: The role of nitric oxide and vitamin D.

BACKGROUND/PURPOSE: Ultraviolet (UV) radiation has both harmful and beneficial effects on human skin and health. It causes skin damage, aging, and cancer; however, it is also a primary source of vitamin D. Additionally, UV radiation can impact energy metabolism and has protective effects on several cardiovascular and metabolic disorders in mice and humans. However, the mechanisms of UV protection against these diseases have not been clearly identified. METHODS: This review summarizes the systemic effects of UV radiation on hypertension and several metabolic diseases such as obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) in mice, and we also consider the mechanisms of action of the related regulators nitric oxide (NO) and vitamin D. RESULTS: UV exposure can lower blood pressure and prevent the development of cardiovascular diseases and metabolic disorders, such as metabolic syndrome, obesity, and type 2 diabetes, primarily through mechanisms that depend on UV-induced NO. UV radiation may also effectively delay the onset of type 1 diabetes through mechanisms that rely on UV-induced vitamin D. UV-induced NO and vitamin D play roles in preventing and slowing the progression of NAFLD. CONCLUSION: UV exposure is a promising nonpharmacological intervention for cardiovascular and metabolic disorders. NO and vitamin D may play a crucial role in mediating these effects. However, further investigations are required to elucidate the exact mechanisms and determine the optimal dosage and exposure duration of UV radiation.

ß-arrestin 2 negatively regulates lung cancer progression by inhibiting the TRAF6 signaling axis for NF-κB activation and autophagy induced by TLR3 and TLR4.

ß-arrestin 2 (ARRB2) is functionally implicated in cancer progression via various signaling pathways. However, its role in lung cancer remains unclear. To obtain clinical insight on its function in lung cancer, microarray data from lung tumor tissues (LTTs) and matched lung normal tissues (mLNTs) of primary non-small cell lung cancer (NSCLC) patients (n = 37) were utilized. ARRB2 expression levels were markedly decreased in all 37 LTTs compared to those in matched LNTs of NSCLC patients. They were significantly co-related to enrichment gene sets associated with oncogenic and cancer genes. Importantly, Gene Set Enrichment Analysis (GSEA) between three LTTs with highly down-regulated ARRB2 and three LTTs with lowly down-regulated ARRB2 revealed significant enrichments related to toll-like receptor (TLR) signaling and autophagy genes in three LTTs with highly down-regulated ARRB2, suggesting that ARRB2 was negatively involved in TLR-mediated signals for autophagy induction in lung cancer. Biochemical studies for elucidating the molecular mechanism revealed that ARRB2 interacted with TNF receptor-associated factor 6 (TRAF6) and Beclin 1 (BECN1), thereby inhibiting the ubiquitination of TRAF6-TAB2 to activate NF-κB and TRAF6-BECN1 for autophagy stimulated by TLR3 and TLR4, suggesting that ARRB2 could inhibit the TRAF6-TAB2 signaling axis for NF-κB activation and TRAF6-BECN1 signaling axis for autophagy in response to TLR3 and TLR4. Notably, ARRB2-knockout (ARRB2KO) lung cancer cells exhibited marked enhancements of cancer migration, invasion, colony formation, and proliferation in response to TLR3 and TLR4 stimulation. Altogether, our current data suggest that ARRB2 can negatively regulate lung cancer progression by inhibiting TLR3- and TLR4-induced autophagy.

A Multi-center Phase II Study Evaluating the Safety and Efficacy of Botulax® in Asian Patients with Benign Masseteric Hypertrophy.

BACKGROUND: Benign masseteric hypertrophy (BMH) is a condition in which the thickness of the masseter muscle is increased, resulting in jawline prominence with undesirable aesthetic appearance. Botulinum toxin type A (BTA) injection is a promising treatment option, but its effective dose remains debated. METHODS: Adults over 19 diagnosed with BMH through visual examination and palpation related to a masseter muscle prominence were selected; 80 patients were randomly assigned into five groups (placebo group and 4 groups with different doses of BTA - 24U, 48U, 72U, 96U on both sides of the jaw) and treated with placebo or BTA once at their baseline visit. During each follow-up, the treatment efficacy was evaluated via ultrasound examination of the masseter muscle, 3D facial contour analysis, visual evaluation by the investigator, and patient satisfaction evaluation. RESULTS: The mean age of the 80 patients was 42.7±9.98 years; 68.75% were women. The mean change of the MMT during the maximum clenching state after 12 weeks of drug administration compared to the baseline in the 24U, 48U, 72U, and 96U groups were -2.33±0.41 mm, -3.35±0.42 mm, -2.86±0.42 mm, and -3.79±0.42 mm. All treatment groups showed a statistically significant decrease compared to placebo. Regarding subjective satisfaction, all treatment groups, except the 24U group at 4 weeks, showed higher satisfaction than the placebo group during all visits. No significant adverse events were noted. CONCLUSIONS: BTA administration of at least 48U for BMH is more cost-effective than high-dose units and has a low possibility of side effects.

FFAR2 antagonizes TLR2- and TLR3-induced lung cancer progression via the inhibition of AMPK-TAK1 signaling axis for the activation of NF-κB.

BACKGROUND: Free fatty acid receptors (FFARs) and toll-like receptors (TLRs) recognize microbial metabolites and conserved microbial products, respectively, and are functionally implicated in inflammation and cancer. However, whether the crosstalk between FFARs and TLRs affects lung cancer progression has never been addressed. METHODS: We analyzed the association between FFARs and TLRs using The Cancer Genome Atlas (TCGA) lung cancer data and our cohort of non-small cell lung cancer (NSCLC) patient data (n = 42), and gene set enrichment analysis (GSEA) was performed. For the functional analysis, we generated FFAR2-knockout (FFAR2KO) A549 and FFAR2KO H1299 human lung cancer cells and performed biochemical mechanistic studies and cancer progression assays, including migration, invasion, and colony-formation assays, in response to TLR stimulation. RESULTS: The clinical TCGA data showed a significant down-regulation of FFAR2, but not FFAR1, FFAR3, and FFAR4, in lung cancer, and a negative correlation with TLR2 and TLR3. Notably, GSEA showed significant enrichment in gene sets related to the cancer module, the innate signaling pathway, and the cytokine-chemokine signaling pathway in FFAR2DownTLR2UpTLR3Up lung tumor tissues (LTTs) vs. FFAR2upTLR2DownTLR3Down LTTs. Functionally, treatment with propionate (an agonist of FFAR2) significantly inhibited human A549 or H1299 lung cancer migration, invasion, and colony formation induced by TLR2 or TLR3 through the attenuation of the cAMP-AMPK-TAK1 signaling axis for the activation of NF-κB. Moreover, FFAR2KO A549 and FFAR2KO H1299 human lung cancer cells showed marked increases in cell migration, invasion, and colony formation in response to TLR2 or TLR3 stimulation, accompanied by elevations in NF-κB activation, cAMP levels, and the production of C-C motif chemokine ligand (CCL)2, interleukin (IL)-6, and matrix metalloproteinase (MMP) 2 cytokines. CONCLUSION: Our results suggest that FFAR2 signaling antagonized TLR2- and TLR3-induced lung cancer progression via the suppression of the cAMP-AMPK-TAK1 signaling axis for the activation of NF-κB, and its agonist might be a potential therapeutic agent for the treatment of lung cancer.

Combined Treatment with Micro-Focused Ultrasound with Visualization and Intradermal Incobotulinumtoxin-A for Enlarged Facial Pores: A Retrospective Study in Asians.

Background: Despite the increasing need for the improvement of enlarged facial pores, the treatment remains challenging. A few previous studies have reported the effects of micro-focused ultrasound with visualization (MFU-V) or intradermal incobotulinumtoxin-A (INCO) on enlarged facial pores. Objective: To evaluate the efficacy and safety of combined treatment with superficial MFU-V and intradermal INCO for enlarged facial pores. Methods: This single-center retrospective study included 20 patients treated with MFU-V and intradermal INCO to improve enlarged facial pores. Outcomes were evaluated 1, 4, 12, and 24 weeks after a single session of the combined procedure. Pore count and density were objectively quantitated using a three-dimensional scanner, and improvement was assessed using the physician and patient Global Aesthetic Improvement Scale (GAIS). Results: The mean pore count and density decreased after one week and decreased by up to 62% until 24 weeks. After one week, almost all patients (100% in physician GAIS and 95% in patient GAIS) showed improvement with a grade 3 (much improved) or higher. All adverse events were transient. Conclusion: Combined treatment with MFU-V and intradermal INCO could be effective and safe for reducing enlarged facial pores; the improvements can be sustained for up to 24 weeks.

T Cell Microvilli: Finger-Shaped External Structures Linked to the Fate of T Cells.

Microvilli are outer membrane organelles that contain cross-linked filamentous actin. Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

Methods to detect AUTOphagy-Targeting Chimera (AUTOTAC)-mediated Targeted Protein Degradation in Tauopathies.

Targeted protein degradation (TPD) facilitates the selective elimination of unwanted and pathological cellular cargoes via the proteasome or the lysosome, ranging from proteins to organelles and pathogens, both within and outside the cell. Currently, there are several in vitro and in vivo protocols that assess the degradative potency of a given degrader towards a myriad of targets, most notably soluble, monomeric oncoproteins. However, there is a clear deficiency of methodologies to assess the degradative potency of heterobifunctional chimeric degraders, especially those in the autophagy space, against pathological, mutant tau species, such as detergent-insoluble oligomers and high-molecular aggregates. The protocol below describes both in vitro and in vivo biochemical assays to induce tau aggregation, as well as to qualitatively and quantitatively measure the degradative potency of a given degrader towards said aggregates, with specific applications of the AUTOTAC (AUTOphagy-TArgeting Chimera) platform provided as an example. A well-defined set of methodologies to assess TPD-mediated degradation of pathological tau species will help expand the scope of the TPD technology to neurodegeneration and other proteinopathies, in both the lab and the clinic. Graphical abstract Overview of assays observing elimination of tauP301L aggregates with AUTOTAC. (A) Description of the biological working mechanism of heterobifunctional chimeric AUTOTAC degraders. (B) Schematic illustration of assays described in this paper.