title: Pathological and clinical aspects of alpha/beta synuclein in Parkinson's disease and related disorders.
abstract: Parkinson's disease (PD) and related synucleinopathies are characterized by extensive neuronal cell loss, which is potentially triggered by α-synuclein misfolding and aggregation. Therefore it is reasonable to suggest that treatments targeting α-synuclein could reduce its levels and toxicity, rescue neuronal cells and halt the neurodegeneration process. Several approaches to decrease α-synuclein levels were employed thus far, mainly by using β-synuclein, another protein from the same family, or immunotherapies. These treatments demonstrated some positive results in preclinical studies, which may pave the road to the development of new promising disease-modifying therapies (DMTs). This approach should be further examined in preclinical and clinical settings, together with a clear process in order to advance candidates, enable the ability to define when there are target engagements and to detect what is a meaningful pharmacological response, and how it will be translated in clinical efficacy.
authors.affiliation: a Specialty Products Department , Dexcel Pharma Technologies Ltd ., Jerusalem , Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Tolmasov
authors.affiliation: b Department of Neurology , Rabin Medical Center, Beilinson Campus , Petach Tikva , Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Djaldetti
authors.affiliation: b Department of Neurology , Rabin Medical Center, Beilinson Campus , Petach Tikva , Israel.
authors.forename: Nirit
authors.initials: N
authors.lastname: Lev
authors.affiliation: a Specialty Products Department , Dexcel Pharma Technologies Ltd ., Jerusalem , Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Gilgun-Sherki
mesh_terms: D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism* / Q000628:therapy; D051844:alpha-Synuclein / Q000378:metabolism*; D051846:beta-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D051846:beta-Synuclein
keywords: Parkinson’s disease; disease-modifying therapy; immunotherapy; multiple system atrophy; α-synuclein; β-synuclein