New Drug Therapies Against Targeting Neurodegenerative Diseases: A Comprehensive Review.

Abstract

Neurodegenerative diseases encompass well-characterized behavioral, cognitive, and movement disorders that affect older people, impacting all facets of daily life. In Alzheimer's disease, specific antibodies targeting the β-amyloid protein (aducanumab, lecanemab, and others) are gaining special interest due to the approval of the first particular drugs against this disease. In Parkinson's disease, most drugs were approved several decades ago; however, new Phase II clinical trials point to monoclonal antibodies as a promising approach, and the report of alkaloids also suggests various therapeutic targets against this disease. Pick's disease has a low prevalence; currently, no drugs are approved by government agencies. However, thanks to molecular tools, it has been possible to elucidate therapeutic targets implicated in the appearance of the disease. α-synuclein is the main therapeutic target in Lewy body disease; most of the reported molecules are in clinical Phases I and II. Additionally, drug repositioning may emerge as a viable option in the search for effective treatments against this disease. In amyotrophic lateral sclerosis, the appearance of newly approved drugs such as tofersen and edaravone, and some others in clinical Phase II (bosutinib), opens a new era in the understanding and treatment of this condition. Altered emotions and progressive damage in some brain regions characterize schizophrenia and vascular dementia. Combinations of tricyclic drugs are a trend that aims to increase the cognitive performance of patients with schizophrenia. In vascular dementia, numerous in vivo trials with molecules of different natures (flavonoids and lactones) have yielded positive results, delaying the progression of the disease. This review examines recent reports on molecules evaluated in vivo and in vitro models of the primary neurodegenerative diseases.