RNA G-quadruplexes and calcium ions synergistically induce Tau phase transition in vitro.

Tau aggregation is a defining feature of neurodegenerative tauopathies, including Alzheimer's disease, corticobasal degeneration, and frontotemporal dementia. This aggregation involves the liquid-liquid phase separation (LLPS) of Tau, followed by its sol-gel phase transition, representing a crucial step in aggregate formation both in vitro and in vivo. However, the precise cofactors influencing Tau phase transition and aggregation under physiological conditions (e.

A cyclic pyrrole-imidazole polyamide reduces pathogenic RNA in CAG/CTG triplet repeat neurological disease models.

Expansion of CAG and CTG (CWG) triplet repeats causes several inherited neurological diseases. The CWG repeat diseases are thought to involve complex pathogenic mechanisms through expanded CWG repeat-derived RNAs in a noncoding region and polypeptides in a coding region, respectively. However, an effective therapeutic approach has not been established for the CWG repeat diseases.

CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome.

Fragile X-related tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease caused by CGG triplet repeat expansions in , which elicit repeat-associated non-AUG (RAN) translation and produce the toxic protein FMRpolyG. We show that FMRpolyG interacts with pathogenic CGG repeat-derived RNA G-quadruplexes (CGG-G4RNA), propagates cell to cell, and induces neuronal dysfunction. The FMRpolyG polyglycine domain has a prion-like property, preferentially binding to CGG-G4RNA.

Identification and immunohistochemical characterization of G-quadruplexes in mouse brain.

Guanine-rich DNA and RNA can form a four-stranded structure, termed G-quadruplexes (G4s) in vitro as well as in cells. The formation of G4 is implicated in many physiological events, such as gene transcription, translation, and epigenetics. However, the presence of G4 has not been revealed in the brain.

Pharmacological prospects of G-quadruplexes for neurological diseases using porphyrins.

Genomic regions with guanine (G)-rich sequences make non-Watson-Crick base pairs, which result in the formation of unique nucleic acid structures called G-quadruplexes (G4s) in cells. Studies have suggested that abnormal G4s are involved in neurological diseases. For example, the formation of G4s caused by expansion of G-rich sequences is implicated in C9orf72-mediated amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), and fragile X-related tremor/ataxia syndrome (FXTAS).

Is 123I-MIBG Scintigraphy Beneficial or Excessive for the Diagnosis of Parkinson's Disease in the Early Phase?

Introduction/objective: In most cases, abnormal cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphy increases the probability of a diagnosis of Parkinson's disease (PD) in patients with parkinsonian features. In our study, we validated the additional value of 123I-MIBG scintigraphy beyond providing information on neurological findings and response to dopaminergic therapy for the diagnosis of PDin the early phase.

Methods: We investigated 77 cases of PD (Hoehn and Yahr Stages I-III) and 73 cases of atypical parkinsonian disorder (APD), including 35 patients with multiple system atrophy, 19 with corticobasal syndrome, and 19 with progressive supranuclear palsy.

Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology.

The most common form of DNA is a right-handed helix or the B-form DNA. DNA can also adopt a variety of alternative conformations, non-B-form DNA secondary structures, including the DNA G-quadruplex (DNA-G4). Furthermore, besides stem-loops that yield A-form double-stranded RNA, non-canonical RNA G-quadruplex (RNA-G4) secondary structures are also observed.