Heterotypic interactions with Aβ42 reshape α-syn aggregation pathways and fibril conformations, generating structurally distinct α-syn fibril populations with different neuronal seeding activities, which provide a molecular framework for understanding how cross-talk between amyloidogenic proteins may contribute to structural and pathological heterogeneity in mixed neurodegenerative diseases.
It is shown that α-synuclein fibrils are more structurally heterogenous than previously believed and that they may continue to remodel their architecture over the course of PD, and fibril assembly pathways and resulting fibril structure are highlighted as critical targets for future therapeutic strategies.
Findings demonstrate that TC modulates both the structural dynamics and functional toxicity of α-synuclein, and highlight its potential as a promising chemical modulator for further investigation in PD-related protein aggregation.
Md Nadir Hassan, Murtaza Hussain, Faisal Nabi et al.· Biochemistry· 0 citations
Based on the structure, a DJ-1-derived peptide (173-180) is designed that significantly inhibited α-synuclein aggregation in TEM and ELISA assays, suggesting its potential as a therapeutic candidate for α-synucleinopathies.
Hyeon Jin Kim, Da Hye Kim, Chang-Woo Han et al.· International Journal of Bio...· 0 citations
The Affinity-directed PROtein Missile system is employed and targeted degradation of α-synuclein impedes the pre-formed fibril (PFF)-induced aggregation of α-synuclein in primary neurons derived from rats expressing human α-synuclein.
Bill Carton, Géraldine Gelders, Gajanan Sathe et al.· npj Parkinson's Disease· 0 citations
The non-amyloid-β component (NAC) region of the Parkinson’s-associated protein α-synuclein plays a key role in its pathogenic aggregation, motivating the development of molecules that target this critical region. Here, we show that a minimal NAC-derived motif, 66VGGAVVT72, can be reprogrammed through backbone engineeri...
Haoliang Zheng, Kyren Miller, Magdalena I. Ivanova et al.· bioRxiv· 0 citations
It is shown that oligomerization drives a transition from dynamic monomers to increasingly ordered intermediates, relevant to models in which α-syn oligomerization alters normal membrane engagement during PD-associated aggregation.
Raya Sadighi, Andrea Istrati, Sigourney Karijodikoro et al.· ACS Central Science· 1 citation
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