Modulating dynamics and function of nuclear actin with synthetic bicyclic peptides.

Actin exists in monomeric globular (G-) and polymerized filamentous (F-) forms and the dynamics of its polymerization/depolymerization are tightly regulated in both the cytoplasm and the nucleus. Various essential functions of nuclear actin have been identified including regulation of gene expression and involvement in the repair of DNA double-strand breaks (DSB). Small G-actin-binding molecules affect F-actin formation and can be utilized for analysis and manipulation of actin in living cells.

Impairment of nuclear F-actin formation and its relevance to cellular phenotypes in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation of lamin A, which contributes to nuclear architecture and the spatial organization of chromatin in the nucleus. The expression of a lamin A mutant, named progerin, leads to functional and structural disruption of nuclear organization. Since progerin lacks a part of the actin-binding site of lamin A, we hypothesized that nuclear actin dynamics and function are altered in HGPS cells.

[Case of obsessive-compulsive disorder associated with neuroleptics-induced deficit syndrome (NIDS): successfully treated by discontinuation of neuroleptics followed by SSRI].

A 59-year-old man, who was being trieated for schizophrenia, exhibited a concurrence of obsessive compulsive (OC) symptoms and neuroleptics-induced deficit syndrome (NIDS). His symptoms were remarkably improved by the discontinuation of neuroleptics followed by the introduction of fluvoxamine. He was originally a prudent, suspicious and unsociable person, the character of which corresponds to a schizotypal personality disorder.