Biomarkers.

Background: Dysfunction of the glymphatic system (GS), a recently discovered brain by-product elimination system, is considered to be one of the pathophysiological mechanisms for common neurodegenerative diseases such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In 2017 a new way to assess the GS was proposed - a diffusion tensor images analysis along perivascular spaces (DTI-ALPS). In our work we evaluated the DTI-ALPS index in groups of patients with AD, DLB, PD and in a comparison group of patients with normal pressure hydrocephalus (NPH).

Biomarkers.

Background: The logopenic variant of primary progressive aphasia (lvPPA) is a disorder centered on language impairment. Alzheimer Disease (AD) is one of the most common underlying pathologies in lvPPA. The aim of our study was to estimate frequency of AD in this phenotype and to analyze clinical features of AD-lvPPA.

Developing Chlorin/Arylaminoquinazoline Conjugates with Nanomolar Activity for Targeted Photodynamic Therapy: Design, Synthesis, SAR, and Biological Evaluation.

In this report, we developed novel chlorin/arylaminoquinazoline conjugates for targeted photodynamic therapy of cancer. The synthesized photosensitizers consisted of chlorin- metallocomplexes (Zn, In, or Pd) conjugated with arylaminoquinazoline ligands with high affinity for epidermal growth factor receptors (EGFR). Additionally, the selectivity and antitumor properties of the conjugates were investigated in the EGFR-expressing A431 human tumor cell line .

Neuroanatomical correlates of language impairment in non-fluent variant of primary progressive aphasia.

Introduction: Non-fluent variant of primary progressive aphasia (nfvPPA) is a neurodegenerative disorder with a predominantly speech and language impairment. Apraxia of speech and expressive agrammatisms along with decreased speech fluency and impaired grammar comprehension are the most typical disorder manifestations but with the course of the disease other language disturbances may also arise. Most studies have investigated these symptoms individually, and there is still no consensus on whether they have similar or different neuroanatomical foundations in nfvPPA.

Analysis of , , , and Gene Expression in the Peripheral Blood of Patients in the Early Stages of Parkinson's Disease.

Parkinson's disease (PD) is one of the most common human neurodegenerative diseases. Belated diagnoses of PD and late treatment are caused by its elongated prodromal phase. Thus, searching for new candidate genes participating in the development of the pathological process in the early stages of the disease in patients who have not yet received therapy is relevant.

Enhancing Precision in Photodynamic Therapy: Innovations in Light-Driven and Bioorthogonal Activation.

Over the past few decades, photodynamic therapy (PDT) has evolved as a minimally invasive treatment modality offering precise control over cancer and various other diseases. To address inherent challenges associated with PDT, researchers have been exploring two promising avenues: the development of intelligent photosensitizers activated through light-induced energy transfers, charges, or electron transfers, and the disruption of photosensitive bonds. Moreover, there is a growing emphasis on the bioorthogonal delivery or activation of photosensitizers within tumors, enabling targeted deployment and activation of these intelligent photosensitive systems in specific tissues, thus achieving highly precise PDT.

A first-in-class β-glucuronidase responsive conjugate for selective dual targeted and photodynamic therapy of bladder cancer.

In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin-e photosensitizer and a derivative of the tyrosine kinase inhibitor cabozantinib, linked by a β-glucuronidase-responsive linker. Upon activation by β-glucuronidase, which is overproduced in various tumors and localized in lysosomes, this conjugate released both therapeutic modules within targeted cells.

Anomia: Deciphering Functional Neuroanatomy in Primary Progressive Aphasia Variants.

Naming decline is one of the most common symptoms of primary progressive aphasia (PPA). Most studies on anomia in PPA are performed without taking into account PPA variants, especially for action naming. Only limited data are available for the neuroanatomical basis of anomia considering differences in the pathogenesis of PPAs.

Analysis of , , , , , and Gene Expression Levels in Peripheral Blood of Patients with Early Stages of Parkinson's Disease.

Parkinson's disease (PD) is a common chronic, age-related neurodegenerative disease. This disease is characterized by a long prodromal period. In this context, it is important to search for the genes and mechanisms that are involved in the development of the pathological process in the earliest stages of the disease.

Gene Methylation in Parkinson's Disease and Multiple System Atrophy.

In recent years, epigenetic mechanisms have been implicated in the development of multifactorial diseases including neurodegenerative disorders. In Parkinson's disease (PD), as a synucleinopathy, most studies focused on DNA methylation of gene coding alpha-synuclein but obtained results were rather contradictory. In another neurodegenerative synucleinopathy, multiple system atrophy (MSA), very few studies investigated the epigenetic regulation.

Mutation analysis of the TATA box-binding protein (TBP) gene in Russian patients with spinocerebellar ataxia and Huntington disease-like phenotype.

Objective: We aimed to analyze the occurrence and clinical and genetic characteristics of spinocerebellar ataxia type 17 (SCA17) among Russian patients with progressive cerebellar ataxia or Huntington disease-like phenotype.

Methods: Genetic analysis of CAG/CAA repeats in TBP gene was carried out in 217 patients, including 153 patients with progressive unspecified ataxia and 64 patients with Huntington disease-like phenotype. SCA types 1, 2, 3, 6 and 8, Friedreich's ataxia, CANVAS and Huntington disease were preliminarily excluded.

Alterations in Proteostasis System Components in Peripheral Blood Mononuclear Cells in Parkinson Disease: Focusing on the HSP70 and p62 Levels.

Parkinson disease (PD) is attributed to a proteostasis disorder mediated by α-synuclein accumulating in a specific brain region. PD manifestation is often related to extraneuronal alterations, some of which could be used as diagnostic or prognostic PD biomarkers. In this work, we studied the shifts in the expression of proteostasis-associated chaperones of the HSP70 family and autophagy-dependent p62 protein values in the peripheral blood mononuclear cells (PBMC) of mild to moderate PD patients.

Reduced Immunosenescence of Peripheral Blood T Cells in Parkinson's Disease with CMV Infection Background.

Immunosenescence is a process of remodeling the immune system under the influence of chronic inflammation during aging. Parkinson's disease (PD) is a common age-associated neurodegenerative disorder and is frequently accompanied by neuroinflammation. On the other hand, cytomegalovirus (CMV), one of the most spread infections in humans, may induce chronic inflammation which contributes to immunosenescence, differentiation and the inflation of T cells and NK cells.

Parkinson's Disease: Available Clinical and Promising Omics Tests for Diagnostics, Disease Risk Assessment, and Pharmacotherapy Personalization.

Parkinson's disease is the second most frequent neurodegenerative disease, representing a significant medical and socio-economic problem. Modern medicine still has no answer to the question of why Parkinson's disease develops and whether it is possible to develop an effective system of prevention. Therefore, active work is currently underway to find ways to assess the risks of the disease, as well as a means to extend the life of patients and improve its quality.

A green synthesis in water of novel (1,5,3-dithiazepan-3-yl)alkanoic acids by the multicomponent reaction of amino acids, CH2O, and 1,2-ethanedithiol.

A library of new (1,5,3-dithiazepan-3-yl)alkanoic acids was prepared by the multicomponent cyclocondensation of amino acids, formaldehyde, and 1,2-ethanedithiol in water at room temperature for 1 to 5 h in high yields. This green procedure offers several advantages such as an operational simplicity, no catalyst, and no production of hazardous materials.

New mutations in the Notch3 gene in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebrovascular small-vessel disease caused by stereotyped mutations in the Notch3 gene altering the number of cysteine residues.

Methods: We directly sequenced exons 2-23 of the Notch3 gene in 30 unrelated Russian patients with clinical/neuroimaging picture suggestive of CADASIL. To confirm the pathogenicity of new nucleotide variants, we used the standard bioinformatics tools and screened 200 ethnically matched individuals as controls.