Parkinson's disease genetics and pathophysiology

GE Vázquez-Vélez, HY Zoghbi - Annual review of neuroscience, 2021 - annualreviews.org
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in …

Alpha-synuclein aggregation pathway in Parkinson's disease: current status and novel therapeutic approaches

M Vidović, MG Rikalovic - Cells, 2022 - mdpi.com
Following Alzheimer's, Parkinson's disease (PD) is the second-most common
neurodegenerative disorder, sharing an unclear pathophysiology, a multifactorial profile …

A single-cell map of antisense oligonucleotide activity in the brain

MA Mortberg, JE Gentile, NM Nadaf… - Nucleic Acids …, 2023 - academic.oup.com
Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly
throughout the central nervous system (CNS). By modulating RNA, they hold the promise of …

Therapeutics in the pipeline targeting α-synuclein for Parkinson's disease

HG Jasutkar, SE Oh, MM Mouradian - Pharmacological reviews, 2022 - ASPET
Parkinson's disease (PD) is the second most common neurodegenerative disorder and the
fastest growing neurologic disease in the world, yet no disease-modifying therapy is …

Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier

SJ Barker, MB Thayer, C Kim, D Tatarakis… - Science Translational …, 2024 - science.org
Antisense oligonucleotides (ASOs) are promising therapeutics for treating various
neurological disorders. However, ASOs are unable to readily cross the mammalian blood …

Evaluating drug targets through human loss-of-function genetic variation

EV Minikel, KJ Karczewski, HC Martin, BB Cummings… - Nature, 2020 - nature.com
Naturally occurring human genetic variants that are predicted to inactivate protein-coding
genes provide an in vivo model of human gene inactivation that complements knockout …

Antisense drugs make sense for neurological diseases

CF Bennett, HB Kordasiewicz… - Annual review of …, 2021 - annualreviews.org
The genetic basis for most inherited neurodegenerative diseases has been identified, yet
there are limited disease-modifying therapies for these patients. A new class of drugs …

Emerging therapeutic strategies for Parkinson's disease and future prospects: A 2021 update

NA Gouda, A Elkamhawy, J Cho - Biomedicines, 2022 - mdpi.com
Parkinson's disease (PD) is a neurodegenerative disorder pathologically distinguished by
degeneration of dopaminergic neurons in the substantia nigra pars compacta. Muscle …

The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils

L Antonschmidt, D Matthes, R Dervişoğlu… - Nature …, 2022 - nature.com
Aggregation of amyloidogenic proteins is a characteristic of multiple neurodegenerative
diseases. Atomic resolution of small molecule binding to such pathological protein …

Who ever said it would be easy? Reflecting on two clinical trials targeting α‐synuclein

PH Jensen, MG Schlossmacher… - Movement …, 2023 - Wiley Online Library
Two recent, high‐profile manuscripts reported negative results with two parallel approaches
of passive immunization targeting α‐synuclein in a population of patients with early …