Recent advances in targeting LRRK2 for Parkinson’s disease treatment.

ingentiumby ingentium

In Parkinson's Disease Literature.

Publication date: Jul 08, 2025

Parkinson’s disease (PD) is a neurodegenerative disease with severe movement problems. Current treatments mainly focus on symptom management by reducing dopaminergic pathways in the brain. Despite these therapies, ongoing disease progression undermines the effectiveness of prevalent approaches, necessitating exploring alternative methods anchored on genetic factors, notably the leucine-rich repeat kinase 2 (LRRK2) gene. Exploring LRRK2 gene pathogenesis has highlighted various mechanisms that may contribute to treating PD, including protein accumulation, altered cytoskeletal dynamics, neuro-inflammation, autophagy, and mitochondrial dysfunction. Based on the findings, there is an actual correlation between elevated levels of LRRK2 and the biomarkers and assays of PD. Furthermore, research results have suggested inhibiting LRRK2 as a therapeutic intervention targeting pathogenic mechanisms with varying degrees of efficacy. Our review wants to understand how LRRK2 works in the body and its relationship with the occurrence of PD by providing biochemical evidence, LRRK2 gene mutations and pathology, and the role of this gene in the immune system. We also discuss targeted therapies such as kinase inhibitors and Proteolysis targeting chimera and the application of using the LRRK2 protein to diagnose PD and develop bioassay designs. Finally, we mention the clinical trials conducted and the challenges and safety required.

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Concepts Keywords
Bioassay Autophagy
Neurodegenerative LRRK2
Parkinson Mitochondrial dysfunction
Relationship Neuro-inflammation
Rich Neurodegenerative diseases
Parkinson’s disease
PROTAC

Semantics

Type Source Name
disease MESH Parkinson’s disease
disease MESH neurodegenerative disease
disease MESH disease progression
drug DRUGBANK L-Leucine
disease MESH pathogenesis
disease MESH inflammation
pathway REACTOME Autophagy
disease MESH mitochondrial dysfunction
pathway REACTOME Immune System
pathway REACTOME Neurodegenerative Diseases
disease MESH neuroinflammation
pathway REACTOME Reproduction
drug DRUGBANK Coenzyme M
disease MESH dementia
disease MESH mutation rate
drug DRUGBANK Rasagiline
drug DRUGBANK Saquinavir
drug DRUGBANK Esomeprazole
disease MESH movement disorder
disease MESH neuron degeneration
drug DRUGBANK Dopamine
disease MESH tremors
disease MESH sleep disorder
disease MESH depression
drug DRUGBANK Nonoxynol-9
disease MESH death
drug DRUGBANK Amino acids
drug DRUGBANK Guanine
disease MESH PARK16
disease MESH uncertainty
pathway REACTOME Macroautophagy
pathway KEGG Lysosome
drug DRUGBANK Calcium
drug DRUGBANK L-Lysine
pathway REACTOME Acetylation
drug DRUGBANK Methylergometrine
disease MESH autoimmune diseases
disease MESH rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
disease MESH celiac disease
disease MESH psoriasis
disease MESH multiple sclerosis
disease MESH oxidative stress
drug DRUGBANK ATP
pathway REACTOME Mitophagy
pathway REACTOME Hemostasis
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
drug DRUGBANK Calcium cation
drug DRUGBANK Niacin
drug DRUGBANK Adenine
drug DRUGBANK Phosphate ion
drug DRUGBANK Potassium Chloride
disease MESH neuroblastoma
drug DRUGBANK Indoleacetic acid
disease MESH Synucleinopathies
disease MESH palsy
disease MESH multiple system atrophy
disease MESH FTLD
drug DRUGBANK Levodopa
disease MESH parkinsonism
disease MESH amyloid plaques
drug DRUGBANK Thiocolchicoside
disease MESH point mutations
drug DRUGBANK Nitrogen
drug DRUGBANK Ubidecarenone
drug DRUGBANK L-Valine
disease MESH stroke
disease MESH thrombosis
pathway REACTOME Apoptosis
drug DRUGBANK Hesperidin
drug DRUGBANK Hydroxyethyl Starch
drug DRUGBANK Glutathione
disease MESH tic
disease MESH carcinoma
disease MESH tumor
drug DRUGBANK Tretamine
disease MESH syndrome
disease MESH demyelination
drug DRUGBANK Trestolone
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH central nervous system disorder
drug DRUGBANK Staurosporine
drug DRUGBANK Sunitinib
drug DRUGBANK Serine
drug DRUGBANK Polyethylene glycol
disease MESH infections
disease MESH leukemia
pathway KEGG Parkinson disease
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK L-Threonine
pathway REACTOME Innate Immune System
pathway KEGG Endocytosis
drug DRUGBANK Iron
disease MESH attention deficit hyperactivity disorder
pathway REACTOME Interferon Signaling
disease MESH neurocognitive disorders
pathway REACTOME Selective autophagy
pathway KEGG Proteasome
drug DRUGBANK Palmitic Acid
disease MESH abnormalities
pathway REACTOME Chaperone Mediated Autophagy
disease MESH brain inflammation
disease MESH Koro
disease MESH colitis
disease MESH leprosy
disease MESH Crohn’s Disease
drug DRUGBANK Guanosine
pathway KEGG mTOR signaling pathway
disease MESH frontotemporal dementia
disease MESH glioblastoma
drug DRUGBANK BENZOTHIAZOLE
disease MESH proteinopathies
drug DRUGBANK Gold
disease MESH renal carcinoma
drug DRUGBANK Istradefylline
drug DRUGBANK L-Tyrosine
pathway KEGG Homologous recombination

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