{"id":55375,"date":"2026-03-19T15:11:33","date_gmt":"2026-03-19T14:11:33","guid":{"rendered":"https:\/\/fgu.cas.cz\/?p=55375"},"modified":"2026-03-19T15:12:59","modified_gmt":"2026-03-19T14:12:59","slug":"a-new-perspective-on-the-early-phase-of-alzheimers-disease-changes-in-the-protective-tau-protein-disrupt-cytoskeletal-protection-and-enable-its-degradation-significance-of-the-study","status":"publish","type":"post","link":"https:\/\/fgu.cas.cz\/en\/2026\/03\/a-new-perspective-on-the-early-phase-of-alzheimers-disease-changes-in-the-protective-tau-protein-disrupt-cytoskeletal-protection-and-enable-its-degradation-significance-of-the-study\/","title":{"rendered":"A new perspective on the early phase of Alzheimer\u2019s disease: Changes in the protective tau protein disrupt cytoskeletal protection and enable its degradation"},"content":{"rendered":"
\n

In the early stages of Alzheimer\u2019s disease, changes occur in a key protein called tau, which normally forms a protective layer around the neuron\u2019s internal skeleton. When modified, tau loses its protective function, leading to neuron death. The new perspective presented by a Czech-French research team uncovers the molecular consequences of tau modifications, opening new avenues for the diagnosis and treatment of early-stage Alzheimer\u2019s disease and related disorders.<\/strong><\/p>\n

Alzheimer\u2019s disease (AD) is a neurodegenerative disorder characterized by the gradual loss of neurons in specific brain regions, resulting in progressive decline of memory, cognition, and self-care abilities.\u00a0Before neuronal degeneration occurs, molecular changes appear in several proteins. One key player is the tau protein\u2014but the precise consequences of its early molecular alterations have remained poorly understood.<\/p>\n

A protective \u201ccoat\u201d that falls apart<\/strong><\/p>\n

Like many other proteins, tau binds to microtubules\u2014the filamentous structures forming the cell\u2019s \u201cskeleton\u201d\u2014and creates a protective coating around them to prevent their disintegration.\u00a0In a new study, researchers from two institutes of the Czech Academy of Sciences, Charles University, and France have described at the molecular level how chemical modification of tau (phosphorylation) disrupts the formation, cohesion, and protective function of tau envelopes, leading to faster microtubule breakdown.\u00a0\u201cOur results show that once tau becomes phosphorylated, the protective envelopes it forms around microtubules lose their ability to safeguard them effectively and become more prone to disruption,\u201d explains Valerie Siahaan, first author of the study from the Institute of Biotechnology CAS.<\/p>\n

Damage begins earlier than expected<\/strong><\/p>\n

A key finding of the study is that microtubules may start to disintegrate even before tau fully detaches from them\u2014a step previously considered essential for disease progression.\u00a0\u201cOur study demonstrates that phosphorylation alone disrupts the internal cohesion of tau envelopes, creating \u2018holes\u2019 that allow enzymes degrading microtubules to penetrate. Thus, microtubule destabilization begins earlier than previously thought, before phosphorylated tau detaches completely and starts to accumulate in neurons,\u201d explains Martin Bala\u0161t\u00edk<\/a>, one of the corresponding authors from IPHYS.<\/p>\n

A new view of the early stage of Alzheimer\u2019s disease<\/strong><\/p>\n

The findings provide a new explanation for one of the hallmarks of Alzheimer\u2019s pathology\u2014the breakdown of microtubules in neurons. The study suggests that this damage may occur early, as a result of the loss of tau\u2019s protective function, rather than only after its complete detachment or the formation of large tau aggregates (neurofibrillary tangles) typical of later disease stages.<\/p>\n

By uncovering the mechanism through which tau phosphorylation undermines microtubule protection, the study opens new paths for exploring the early molecular events in Alzheimer\u2019s disease and related disorders\u2014and potentially for developing therapeutic strategies focused on preserving neuronal stability.<\/p>\n

The work was carried out in international collaboration between scientists from the Institute of Biotechnology CAS, the Institute of Physiology CAS, Charles University in Prague, and the Institut Curie in France, and was published in\u00a0Nature Chemical Biology<\/em>.<\/p>\n

Reference:<\/strong>
\nSiahaan V., Weissova R., Karhanova A., Lanska E., Ruiz-Estrada M. J., Pukajova B., Dostal V., Henriot V., Janke C., Libusova L., Braun M., Balastik M., and Lansky Z.\u00a0Tau phosphorylation impedes functionality of protective tau envelopes.<\/em>\u00a0Nat Chem Biol<\/em>\u00a0(2026). IF = 15.7; DOI:\u00a010.1038\/s41589-025-02122-9<\/span><\/a><\/p>\n<\/blockquote>\n","protected":false},"excerpt":{"rendered":"

In the early stages of Alzheimer\u2019s disease, changes occur in a key protein called tau, which normally forms a protective layer around the neuron\u2019s internal skeleton. When modified, tau loses its protective function, leading to neuron death. The new perspective presented by a Czech-French research team uncovers the molecular consequences of tau modifications, opening new […]<\/p>\n","protected":false},"author":11,"featured_media":55404,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[113],"tags":[],"class_list":["post-55375","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-important-success"],"acf":[],"_links":{"self":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/posts\/55375","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/users\/11"}],"replies":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/comments?post=55375"}],"version-history":[{"count":0,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/posts\/55375\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/media\/55404"}],"wp:attachment":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/media?parent=55375"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/categories?post=55375"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/tags?post=55375"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}